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*
Laboratoire Associé Institut National de la Recherche Agronomique d’Immunologie Parasitaire, Faculté de Pharmacie, Tours, France; and
Department of Medicine and Microbiology, Dartmouth Medical School, Hanover, NH 03756
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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4 and
anti-E Abs partially inhibited IEL intestinal
homing. The Ab treatment dramatically impaired resistance to a
subsequent oral infection. These finding indicate that lymphocyte
homing is an important parameter in establishing long term immunity to
recurrent infection with this parasite. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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ß-chains or homodimeric -chains. Of the CD8 population,
40% are 
TCR+ and 20% are ß TCR. IEL
provide a number of important immunological functions including
cytotoxic activity (1, 2); secretion of cytokines including IL-2, IL-3,
IL5, TNF-, TGF-ß, and IFN- (3, 4); as well as modulation of
epithelial cell death and regeneration.
Infection with T. gondii in humans and other
mammals is acquired via oral ingestion of tissue cysts containing
bradyzoites from infected meat or oocysts containing sporozoites from
contaminated soil. Previous observations from our laboratories have
demonstrated an essential role for intestine-derived mucosal immunity
against this parasite. IEL isolated from orally infected mice exhibit
Ag-specific CTL activity in vitro (5). Moreover, adoptive transfer of
these Ag-primed IEL into the naive host protects against a lethal
parasite challenge (6). Recently, we demonstrated that Ag-primed IEL
provide long term protection following lethal parasite challenge as
determined by reduced mortality and decreased number of brain cysts in
the recipient. The protective IEL are
CD8+ß+, ß TCR. Protection is
partially dependent on the presence of intact TCR as well as
endogenous production of IFN- (6, 7) in the host. Increased
expression of the activated memory T cell phenotype, in particular
Ly-6C, was noted in the protective IEL cell population.
Activated T cells traffic to the intestine although the molecular
mechanisms that allow for this migration are not fully appreciated.
Several integrins and chemokines including crg-2 and MuMig may enhance
the mobilization of CD8 T cells into intestinal mucosa (8, 9, 10, 11). The
Eß7 integrin is strongly expressed by IEL
(9, 12, 13). This ligand is involved in the binding of IEL to
epithelial cells via interaction with E-cadherin (14, 15). The IEL
deficiency associated with a lack of ß7 expression would
suggest that Eß7 is required for entry and
or retention of T cells in the intestinal epithelium (16, 17). T cell
activation results in the accumulation of
Eß7 high cells in the mesenteric lymph
nodes, lamina propria, and IEL compartment suggesting a role for this
molecule in lymphocyte homing. Another integrin,
4ß7, expressed in low frequency on IEL is
evident on lamina propria lymphocytes and on 50% of T cells.
Activated lymphocytes expressing 4ß7 can
bind to several receptors, the most prominent of which is MadCAM-1, a
protein expressed by high endothelial venule in Peyer’s patches and
mesenteric lymph nodes and the flat endothelium in the lamina propria
(18, 19). Recent studies indicate that the interactions of
4ß7 and MadCAM-1 play a major role in
lymphocyte homing to Peyer’s patches, lamina propria, and mesenteric
lymph nodes (20). In this study, we report that Ag-primed IEL traffic
to a wide range of host organs following adoptive transfer by i.v.
administration. Protection against lethal challenge is dependent on the
ability of these lymphocytes to traffic to the intestine and other host
organs.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Female 8–10-wk-old inbred CBA/J (H-2k) mice were obtained from Janvier Breeding Center (Le Genest St. Isle, France) and congenic Thy-1.1 and Thy-1.2 C57BL/6 mice were purchased from The Jackson Laboratory (Bar Harbor, ME). Strain 76K of T. gondii was used in this study. This strain produces large numbers of cysts containing bradyzoites in the brains of infected mice. Mice were infected perorally by intragastric gavage of cysts collected from the brains of infected mice. Cysts are maintained by passage every 2 mo into naive mice. Brain tissue containing strain 76K cysts was suspended in saline buffer, and the suspension was adjusted to contain 100 or 40 cysts in each 0.5-ml dose to infect the CBA/J or Thy-1.2 C57BL/6 donor mice, respectively. The recipient mice were intragastrically challenged with 100 cysts for CBA/J and 40 for Thy-1.1 C57BL/6 mice, 3 days following the IEL passive transfer.
Isolation of IEL and subset purification
IEL were isolated as previously described with modification (21). The small intestine was flushed with PBS and cut into 2-mm sections. After removal of the Peyer’s patches and fat, the intestine was divided longitudinally. The mucosa were scraped and dissociated by mechanical disruption on a stirring platform for 15 min in RPMI 1640 containing 4% FCS and 1 mM dithioerythritol. Tissue debris and cell aggregates were removed by passage over a glass wool column in RPMI 1640–4% FCS. The lymphocytes were obtained by centrifugation on a Ficoll layer (d = 1.077) and the cells were suspended in complete medium. Primed IEL were collected at day 13 and day 9 after oral infection of the CBA/J and C57BL/6 donor mice, respectively. Control unprimed IEL were obtained from uninfected mice.
Splenocytes were prepared at the same time (day 13 after infection of CBA mice) from primed donors and were used as control cells in short term homing experiments.
IEL were resuspended in RPMI with 4% FCS and washed before separation. Thirty million cells were incubated with rat anti-mouse CD8ß mAb (PharMingen, San Diego, CA) for 30 min at 4°C followed by 15 min of incubation at 4°C with goat anti-rat IgG microbeads. The complexes were applied to a prewashed miniMACS (Miltenyi Biotec, Bergisch Gladbach, Germany) column in PBS plus 10% FCS. Both positive and negative IEL fractions were assayed. Cells were stained with FITC-conjugated rat anti-CD8ß mAb and analyzed by FACS. This purification procedure produced a highly pure CD8ß+ population (>98%).
Immunfluorescence staining
Cell suspensions containing 2 x 106 cells were
added to 96-well plates and washed twice in PBS. The cells were
resuspended in 50 µl of normal rabbit serum for 10 min at room
temperature to prevent nonspecific Ab staining. The cells were then
incubated for 1 h on ice in the presence of FITC-labeled rat mAb
(1:1000 dilution) directed at Thy-1.2, CD8, CD8ß. Cell surface
phenotype of IEL were also assayed for expression of
4ß7 and Eß7,
the homing integrins. To accomplish this, 4 and
E molecules were tagged with the purified PS/2 from rat
(American Type Culture Collection, Manassas, VA) and the 2E7 from
hamster mAbs, respectively (gift from L. Lefrançois) (22, 23).
PS/2 and 2E7 were produced by culture of the hybridoma cells and
purified by protein G affinity chromatography. After incubation with
the latter, the appropriate FITC conjugate (anti-rat or
anti-hamster) were used as a secondary reagent for detection. After
staining, the cells were washed and fixed with 1% paraformaldehyde
buffer and analyzed by FACScan (Becton Dickinson, Mountain View, CA)
the following day.
Short term homing
Purified IEL (1 x 107) were labeled with 50 µCi of 51Cr per ml for 1 h at 37°C. Nonincorporated 51Cr was removed by centrifugation. After washing, 1 x 107 IEL were injected into the tail vein of recipient mice. The recipient mice were sacrificed 2 h after the transfer. Blood was collected, and intestine, lungs, kidneys, liver, spleen, brain, mesenteric lymph nodes, and peripheral lymph nodes were removed. Peripheral lymph nodes removed comprised the superficial inguinal nodes, the brachial and popliteal nodes, the superficial cervical nodes, and the iliac lymph nodes. All the Peyer’s patches were collected from the intestine. Intestines were washed by flushing 20 ml of buffer. Organs were carefully homogenized in 3 ml of water-1% Triton X-100, and radioactivity was counted from all the organs in a gamma counter. Values were expressed as percentage of radioactivity recovered in the organ and the remaining body. Two mice were used in each experiment, and each experiment was repeated at least three times.
Because of the spontaneous release, the chromium study could not last more than some hours. To study IEL trafficking after 2 h, a fluorescent assay was conducted. IEL from naive or 13-day-infected CBA/J mice were resuspended in PBS (1 x 107/ml) and stained with 5-(and -6-)-carboxyfluorescein diacetate, succimidyl ester (CFSE) as described elsewhere (24). Briefly, aliquots of 1 x 107 cells were labeled with 5 mM CFSE for 15 min at 37°C. Labeling was stopped by adding cold PBS-10% FCS. Cells were washed twice with cold PBS-10% FCS and resuspended in PBS before injection. IEL (1 x 107) were injected i.v. into naive recipient mice. The recipient mice were sacrificed 24 h after the transfer and IEL were isolated from their intestine. Cell suspensions were also prepared from Peyer’s patches, mesenteric lymph nodes, spleen, lungs, liver, kidneys, and heart. Fluorescence from all these organs was analyzed by FACS. Six recipient mice were used in each group. Results are expressed as the percentage of tagged IEL recovered in the organs compared with the injected population.
Long term homing
Congenic C57BL/6 mice were also utilized to determine whether the adoptively transferred IEL persist in the recipient host mice. In this experiment, IEL from Thy-1.2 C57BL/6 mice were isolated at day 9 postinfection (pi) and transferred (2 x 106) into Thy-1.1 recipients. Three days after the transfer, mice were challenged. Homing was assessed by phenotypic analysis for Thy-1.2 expression in various organs including the intestine at increasing time points before or after the challenge. Control included a phenotypical analysis within the untransferred Thy-1.1 mice. Six mice were used in each group.
Homing blocking
IEL were collected either from infected CBA or Thy-1.2 mice.
Chromium-labeled or unlabeled purified IEL were incubated
simultaneously with 50 µg of anti-4 and 50 µg of
anti-E mAbs (30 min, 37°C). At the very moment of
the tail vein injection into recipient mice (CBA or Thy-1.1), 400 µg
of each purified mAb were added to the IEL suspension. Two hours after
the transfer, mice that had received the 51Cr-labeled cells
were killed, and intestine homing was assessed as previously described.
CBA mice that were transferred with unlabeled cells were challenged and
treated every 3 days until day 15 after the transfer with 200 µg of
each Ab administered by i.p. injection. Thy-1.1 mice transferred with
treated or untreated Thy-1.2 IEL received i.p. injection of mAbs as
described above and were killed 8 days after the challenge. Their IEL
and mesenteric lymph nodes were isolated and analyzed for Thy-1.2 cells
as previously described. Control groups included mice sham treated with
irrelevant Abs (Sigma Chemical, St. Louis, MO, for rat and PharMingen
for hamster Ig), mice transferred with unprimed IEL and challenged, and
mice untransferred and unchallenged but treated with the same amount of
mAbs.
To study the consequence of trafficking blocking of endogenous cells, untransferred mice were challenged and injected in the same way with the two mAbs. In that case, control mice were challenged but not treated with the Abs. Whatever the group or the experiment, mice were sacrificed 1 month after the challenge and brain cysts were enumerated. Six mice were used in each group, and each experiment was performed three times.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Our previous observations indicated that primed IEL were
protective against parasite challenge when adoptively transferred into
naive mice. A radioisotope trafficking study was done to determine
whether Ag-primed IEL home to the intestine and other host organs. Two
hours after the i.v. injection of 51Cr-labeled primed IEL
(1 x 107), 22% of the total radioactivity was
detected in the small intestine of the recipient mice (Fig. 1
). Increased radioisotope activity was
observed in the liver (22%), spleen (15%), lungs (24%), and kidneys
(15%) but not within the central nervous system (<2%). The level of
radioactivity was 2% or less in other immune compartments of the
intestine including Peyer’s patches (<1%), mesenteric lymph nodes
(2%), superficial lymph nodes (iliac, inguinal, brachial, and
retrocervical), and blood. In comparison, Ag-primed splenocytes traffic
preferentially to the spleen rather than the intestine. For example,
following splenocyte transfer, most of the radioactivity was recovered
in either the spleen (37%) or the lungs (35%); whereas only 5% of
the splenocyte radioactivity was detected in the intestine (Fig. 1).
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In the spleen, 20% of the total radioactivity could be observed in
recipient mice. There was no significant difference in the radioactive
counts observed in the other organs between mice receiving Ag-primed vs
unprimed IEL.
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). This confirmed that primed IEL
displayed the more efficient intestine-selective trafficking pattern.
The day after transfer, primed IEL could be recovered from the Peyer’s
patches (17%) and mesenteric lymph nodes (20%) of the recipients. In
comparison, <2% of the IEL could be detected in these organs at
2 h posttransfer. Unprimed IEL could be detected in the mesenteric
lymph nodes 1 day after transfer (30%) but not in the Peyer’s patches
(Table I).
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ß home preferentially to the intestine
To determine the preferential homing of specific CD8+
subpopulations to the intestine, IEL were isolated from infected mice
and separated into their respective CD8ß+ and
CD8ß- subsets. We observed that both the
CD8ß+ and CD8ß- subsets home to the
intestine following adoptive transfer via i.v. administration. There
was, however, a preferential increase in the homing ability of
Ag-primed CD8ß+ (26%) compared with primed
CD8ß- (17.5%) to the intestine (Fig. 3). Also noted was an increase in the
number of CD8ß- in the spleen, liver, and lungs compared
with CD8ß+.
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4 and E molecules and
their role in the homing
The involvement of the integrins 4ß7
and Eß7 in trafficking of the lymphocytes
to the intestine was evaluated. For these studies, IEL were isolated at
varying time intervals pi and assayed for ligand expression. An
increase in the expression of E molecule was observed on
the purified IEL at day 3 pi. By day 13 pi, 90% of the IEL were
E+ and 50% expressed
4+ (Fig. 4).
Our previous studies had indicated that optimal protection occurred
when IEL were harvested from infected CBA mice at day 13 pi. Phenotypic
analysis of the IEL subsets at day 13 revealed that
E+ expression was increased in both
CD8b- and CD8ß+ population. There was a
corresponding decrease in the expression of 4 in the
CD8ß-. At day 13 pi, 81 and 60% of the primed
CD8ß+ population were respectively expressing the
4 and E molecules and 58.5 and 84% of
the primed CD8ß- were respectively expressing the
4 and E molecules.
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4ß7 and
Eß7 in lymphocyte trafficking, IEL were
first incubated with anti-4 and
anti-E mAbs and then transferred into naive
recipient mice. At 2 h posttransfer (Fig. 5), nearly 50% of the Ab-treated IEL
were unable to home to the intestine as determined by radioactive
count. Same results were obtained with anti-4 alone
(data not shown).
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A genetic approach was utilized to evaluate IEL homing in long
term immunity to the parasite. For this, primed IEL from C57BL/6
Thy-1.2+ donor mice, infected 9 days before, were
adoptively transferred into congenic C57BL/6 Thy-1.1+ mice.
At that time, IEL from C57BL/6 mice displayed the maximum protective
capacity (7). Cells from the isolated organs were recovered and
analyzed by FACS for expression of Thy-1.2+. As shown in
Fig. 6, at the time of parasite challenge
(day 0) which corresponded to 3 days posttransfer, 8% of the purified
IEL from the intestine of the recipient Thy-1.1 expressed
Thy-1.2+. Also noted was a 10% increase of the Thy-1.2
phenotype in the mesenteric lymph nodes. At 3 days postchallenge, a
decline in the expression of Thy-1.2+ type cells in all
organs assayed was observed. At 8 days postchallenge,
Thy-1.2+-expressing cell populations increased in the
intestine (16%) and the mesenteric lymph nodes (30%). Treatment of
Ag-primed IEL with Ab to E and 4
inhibited the trafficking of these cells to the intestine at day 8
postchallenge (Fig. 7).
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An inhibition assay was performed to determine whether
4 and E have a functional role in host
protection against infection. For this study, anti-4
and E Abs were administered to recipient mice 1 day
before and every 3 days after adoptive transfer of Ag-primed IEL.
Preliminary data indicated that exposure to anti-4
and -E alone had a nominal effect on host susceptibility
to infection. Protection was evaluated by enumeration of brain cysts in
the survivors at 30 days postchallenge. As shown in Table II, Ab treatment directed at
4 and E abrogated the protection
conferred by the transfer of primed IEL. In comparison, control mice
that received primed IEL without blocking Ab were protected against the
challenge as measured by the number of brain cysts.
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4 and
anti-E Ab and challenged with an oral dose of
parasites. As illustrated in Table III,
treatment with the blocking Abs to these integrins significantly
(p < 0.05) impaired resistance to primary
infection. There was no effect of these Abs on either the
CD4+ or the CD8+ population from the spleen,
mesenteric lymph nodes, and intestine of uninfected mice.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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4ß7 and Eß7,
are associated with the lymphocyte trafficking response in this model,
since blocking of these molecules increases host susceptibility to
parasite challenge. Once ingested T. gondii invades the intestinal epithelial cells and is disseminated to a variety of organs including muscle and the central nervous system. Thus, an intact mucosal surface replete with Ag-primed immune cells is essential for long term protection against recurrent infection in all mammals. Previous studies in our laboratories have demonstrated that T. gondii-primed IEL, when passively transferred into naive mice, confer complete protection against an orally administered lethal parasite challenge (6). We observed that splenocytes preferentially home to the spleen whereas adoptively transferred intestine-derived IEL traffic to the intestine, although increased numbers of these cells could also be found within the spleen and other organs posttransfer. The increased activity within the liver and lungs following i.v. administration of IEL is consistent with earlier observations (20). The increase in cell number within these organs can be explained by either the clearance of damaged cells or perhaps physiological recirculation that may occur within these organs (26).
Ag-stimulated lymphocytes display tissue-selective trafficking patterns (25, 27). Our studies indicate that primed IEL traffic efficiently to the intestine when administered by i.v. injection. Analysis with the fluorescent tagged IEL as well as the phenotype analysis within the congenic mouse model establish that adoptively transferred IEL could be recovered from the mesenteric lymph nodes and the Peyer’s patches posttransfer, although little recovery of the IEL was apparent at 2 h posttransfer. Recently, it has been shown by in vitro culture that IEL that migrate through the intestine epithelial cell monolayer and settle among the enterocytes depart the monolayer within 24 h (28). Thus, the IEL that traffic to the intestine within 2 h may disseminate to other organs, in particular the Peyer’s patch and mesenteric lymph nodes. Similarly, IEL located within the spleen, lung, and liver may traffic to other immune compartments as well as mesenteric nodes and Peyer’s patch at a further time point, such as 24 h posttransfer. Although T. gondii-primed IEL can migrate from the intestine, our study in congenic mice illustrated that IEL traffic back to the intestine after Ag reexposure. It is this recirculation that is probably critical for the establishment of long term immunity to reinfection.
We observed that both primed CD8ß+ and
CD8ß- T cells traffic to the intestine although
CD8ß+ are perhaps more efficient. Previous observations
indicate that it is the CD8 ß+ T cell population that is
responsible for increased survival against a lethal parasite challenge
and the establishment of long term immunity. Memory T cells expressing
4ß7 recirculate selectively through the
intestine (29) and Peyer’s patches (27). Lymphocytes expressing the
phenotypes CD44high, CD4+, or B220+
may exhibit up-regulation of 4ß7 and are
involved in intestine trophism as well as immunity to enteric pathogens
such as rotavirus (30, 31, 32). We observed that both CD8ß+-
and CD8ß--primed IEL express an 4
molecule, although CD8ß+ express this molecule in higher
proportion. Our data suggest that it is the trafficking and
recirculation of the CD8ß+ IEL that is responsible for
long term protection.
It appears that at least two integrin ligands (4 and
E) are required for the homing process. Interaction of
the MAdCAM-1 molecule on the mucosal surface with its integrin ligand,
4ß7, on the lymphocyte allows for the
selective recruitment of these cells to intestinal sites (18, 20, 33).
We observed high expression of 4 on IEL isolated from
the intestine of infected mice. Exposure of either the recipient mouse
or Ag-primed IEL to anti-4 mAb, in combination with
anti-E mAb partially blocked IEL intestine homing
and increased susceptibility following parasite challenge. Treatment
with anti-E alone did not impair the trafficking of
IEL, and as one-half of the IEL were expressing the 4
molecule at the time of the transfer, the blocking effect could not be
complete. This suggested that other molecules are probably involved in
the homing. Although MAdCAM receptor can be identified among the
sinus-lining cells closest to the lymphoid white pulp of the spleen, Ab
to its ligand 4ß7 was insufficient to
prevent IEL trafficking to the spleen. This is consistent with the
reports of others that demonstrate that blocking of 4
and other integrins (e.g. VLA-4, VCAM-1, and L-selectin) can inhibit
lymphocyte trafficking into inflammatory tissue but has either no
effect or causes a paradoxical increase on lymphocyte trafficking into
the spleen (20, 34).
Eß7 is the predominant cell adhesion
molecule on the surface of intestine-derived IEL. There is a
substantial increase in the number of intestine IEL expressing
E molecule after T. gondii infection.
The predominant functional role of Eß7 is
to retain lymphocytes within or closely apposed to epithelial cells.
For IEL, Eß7 and E-cadherin interaction
may be an important signaling event between T cells and epithelial
cells. Ab cross-linking of Eß7 can trigger
the TCR and provide a potent costimulation for IEL proliferation,
cytokine secretion (36), and mucosal CTL activity against colorectal
cancer cells (15, 37). Previous studies from our group demonstrate that
it is the IEL isolated at day 13 postinfection that exhibit the
greatest protective and CTL function against parasite-infected target
cells. By FACS analysis, we observed that expression of the
E molecule was greatest among the primed IEL population.
Synthesis of the E subunit is induced by TGF-ß
cytokine (23, 35). This cytokine is abundant in the intestinal
epithelial cells, especially those in the distal region of the villus,
and induces E synthesis in T cells on their arrival in
the epithelial microenvironment. During this period, the
4 subunit is down-regulated on IEL and almost replaced
by E as a partner for ß7. Preliminary data
in our laboratory indicate that the IEL obtained from orally infected
mice produce substantial quantities of TGF-ß.
There is potential importance for expression of these integrins in host
immunity to this enterically derived pathogen. Since IEL are cytotoxic
for T. gondii-infected enterocytes in vitro (5),
Eß7 may play an integral role in that
interaction. Further, this ligand may be important in cell-cell
signaling between the IEL and the enterocyte. The integrin could
provide a means by which T cells directly influence fundamental aspects
of epithelial cell function. Intestinal epithelial cells down-regulate
IEL (38) and may be involved in the extensive intestinal
hyperinflammatory response that we and others have observed in certain
strains of mice (39, 40). IEL produce chemoattractant mediators or
chemokines that may initiate or modulate the immune response
against T. gondii at the mucosal level (41).
Taken together, our data suggest that Ag-primed IEL can traffic to the
intestine and stimulate long term immunity to reinfection. The ability
of these cells to traffic to the intestine is dependent on the
expression of the appropriate integrins which if blocked increases
susceptibility to parasite challenge. If 4 molecule
seems involved in IEL trafficking as already described by others (20),
the interaction of the E molecule with its receptor the
E-cadherin appears necessary for the IEL to fully express their
protective abilities. Further studies are currently under way to
determine the mechanism by which these IEL regulate the host immune
response to the parasite at the mucosal level.
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Dominique Buzoni-Gatel, Laboratoire Associé Institut National de la Recherche Agronomique d’Immunologie Parasitaire, Faculté de Pharmacie, 31 avenue Monge, 37200 Tours, France. E-mail address:
3 Abbreviations used in this paper: IEL, intraepithelial lymphocytes; CFSE, 5-(and -6-)-carboxyfluorescein diacetate, succimidyl ester; pi, postinfection.
Received for publication December 4, 1998. Accepted for publication March 1, 1999.
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References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
ß-CD8+, but not -CD8+, TCR-ß+ murine intestinal intraepithelial lymphocytes can mediate perforin-based cytotoxicity, whereas both subsets are active in Fas-based cytotoxicity. J. Immunol. 156:35.[Abstract]
, TNF) in the induction of epithelial cell death and renewal. Eur. J. Immunol. 28:730.[Medline]
/ß+ Thy-1+ gut intraepithelial lymphocytes, lytic for parasite-infected enterocytes. J. Immunol. 153:4596.[Abstract]
T cells: implications for the recruitment of inflammatory cells to damaged epithelia. J. Immunol. 157:985.[Abstract]
chain. Eur. J. Immunol. 22:885.[Medline]
Eß7. Biochem. Soc. Trans. 25:433.[Medline]
M290ß7 recognizes a ligand on mucosal epithelial cell lines. Eur. J. Immunol. 23:1630.[Medline]
4ß7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74:185.[Medline]
4 integrins in lymphocyte homing to mucosal tissues in vivo. J. Immunol. 152:3282.[Abstract]
4ß7 correlates with the ability of CD8+ memory T cells to clear rotavirus infection. J. Virol. 72:726.4ß7 on a subset of human CD4+ memory T cells with hallmarks of gut-trophism. J. Immunol. 151:717.[Abstract]
4ß7. J. Immunol. 161:4227.4 integrin. J. Immunol. 151:4790.[Abstract]
E on lymphocytes is not associated with mucosa-specific homing. Eur. J. Immunol. 25:1487.[Medline]
1+ lymphocytes recognize tumor cells of epithelial origin. J. Exp. Med. 183:1681.-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J. Exp. Med. 184:597.This article has been cited by other articles:
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  D. Bernard, A. Six, L. Rigottier-Gois, S. Messiaen, S. Chilmonczyk, E. Quillet, P. Boudinot, and A. Benmansour Phenotypic and Functional Similarity of Gut Intraepithelial and Systemic T Cells in a Teleost Fish J. Immunol., April 1, 2006; 176(7): 3942 - 3949. [Abstract] [Full Text] [PDF]
|
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C. E. Egan, J. E. Dalton, E. M. Andrew, J. E. Smith, M.-J. Gubbels, B. Striepen, and S. R. Carding A Requirement for the V{gamma}1+ Subset of Peripheral {gamma}{delta} T Cells in the Control of the Systemic Growth of Toxoplasma gondii and Infection-Induced Pathology J. Immunol., December 15, 2005; 175(12): 8191 - 8199. [Abstract] [Full Text] [PDF]
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 B. A. Leav, M. Yoshida, K. Rogers, S. Cohen, N. Godiwala, R. S. Blumberg, and H. Ward An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control of Cryptosporidium parvum Infection in Mice Infect. Immun., December 1, 2005; 73(12): 8425 - 8428. [Abstract] [Full Text] [PDF]
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 H. Mizubuchi, T. Yajima, N. Aoi, T. Tomita, and Y. Yoshikai Isomalto-Oligosaccharides Polarize Th1-Like Responses in Intestinal and Systemic Immunity in Mice J. Nutr., December 1, 2005; 135(12): 2857 - 2861. [Abstract] [Full Text] [PDF]
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 J-K Kim, M Takeuchi, and Y Yokota Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice Gut, April 1, 2004; 53(4): 480 - 486. [Abstract] [Full Text] [PDF]
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 D. G. Mordue and L. D. Sibley A novel population of Gr-1+-activated macrophages induced during acute toxoplasmosis J. Leukoc. Biol., December 1, 2003; 74(6): 1015 - 1025. [Abstract] [Full Text]
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C. Bonenfant, I. Dimier-Poisson, F. Velge-Roussel, D. Buzoni-Gatel, G. Del Giudice, R. Rappuoli, and D. Bout Intranasal Immunization with SAG1 and Nontoxic Mutant Heat-Labile Enterotoxins Protects Mice against Toxoplasma gondii Infect. Immun., March 1, 2001; 69(3): 1605 - 1612. [Abstract] [Full Text] [PDF]
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L. H. Kasper and D. Buzoni-Gatel Ups and Downs of Mucosal Cellular Immunity against Protozoan Parasites Infect. Immun., January 1, 2001; 69(1): 1 - 8. [Full Text] [PDF]
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 D. J. Manfra, S.-C. Chen, T.-Y. Yang, L. Sullivan, M. T. Wiekowski, S. Abbondanzo, G. Vassileva, P. Zalamea, D. N. Cook, and S. A. Lira Leukocytes Expressing Green Fluorescent Protein as Novel Reagents for Adoptive Cell Transfer and Bone Marrow Transplantation Studies Am. J. Pathol., January 1, 2001; 158(1): 41 - 47. [Abstract] [Full Text] [PDF]
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F. Velge-Roussel, P. Marcelo, A. C. Lepage, D. Buzoni-Gatel, and D. T. Bout Intranasal Immunization with Toxoplasma gondii SAG1 Induces Protective Cells into Both NALT and GALT Compartments Infect. Immun., February 1, 2000; 68(2): 969 - 972. [Abstract] [Full Text] [PDF]
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