| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Dermatology and
Pathology, University Hospital of Zürich, Zürich, Switzerland; and
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-1,3-fucosyltransferase VII (FucTVII)-/- are
characterized by deficiency of E-, P-, and L-selectin ligand activity.
This model system was used to evaluate the role of the interactions of
selectins with their ligands in T and B cell responses. In the present
study, FucTVII-/- mice showed reduced CD4+ T
cell-mediated contact hypersensitivity reactions of the ears to FITC as
well as reduced CD8+ T cell-mediated delayed-type
hypersensitivity reactions of the footpads against lymphocytic
choriomeningitis virus infection. As Langerhans cell migration to local
lymph nodes as well as CD4+ and CD8+ T cell
induction were found to be normal, the afferent arm of these reactions
was not impaired. The reduced inflammatory reactions of the skin were
due to inefficient lymphocyte extravasation into the skin. In contrast,
extravasation of CD4+ and CD8+ T cells into
visceral organs, such as the ovaries or the brain, was not impaired in
FucTVII-/- mice. Elimination of vaccinia virus and of
lymphocytic choriomeningitis virus from ovaries and brain, as well as
elimination of tumor cells from several visceral organs was normal.
Thus, interactions of selectins with their ligands are important for
lymphocyte homing into the skin, but not for lymphocyte extravasation
into visceral organs. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The synthesis of fucosylated glycans, which form part of the ligands
for E-, P-, and L-selectin, is catalyzed by a series of glycosylation
reactions. The final reaction of this pathway is controlled by specific
-1,3-fucosyltransferases (9).
Mice genetically manipulated to lack expression of fucosyltransferase
VII were found to be deficient in E-, P-, and L-selectin ligand
activity (10). These mice have previously been shown to
exhibit compromised leukocyte extravasation using a chemical
peritonitis model, as well as reduced cell numbers in their lymph
nodes, suggesting a leukocyte-trafficking defect (10).
Deficiency of E- and P-selectin ligands on Th1 and T cytotoxic 1
lymphocytes was demonstrated to annul trafficking of these T cells to
inflamed cutaneous sites, as demonstrated by the absence of cutaneous
hypersensitivity to 2,4-dinitrofluorobenzene in
-1,3-fucosyltransferase VII (FucTVII)-/-
mice (11). The present study uses viral model systems to
assess CD4+ and CD8+ T cell
function in vivo.
The lymphocytic choriomeningitis virus (LCMV) model is used to analyze CD8+ T cell function in vivo. The arenavirus LCMV is a natural mouse pathogen (12). The virus replicates at the site of inoculation, but does not cause tissue damage, since LCMV is noncytopathic. Within 8 days, wild-type (wt) mice generate a strong CD8+ cytotoxic T cell response in the lymph nodes and the spleen (12). These CD8+ effector T cells eliminate the virus via a perforin-dependent mechanism (13), causing immunopathological tissue damage (12). Induction of CD8+ CTL and elimination of the virus are independent of CD4+ T cells, and the role of Abs can be neglected (12).
Vaccinia virus (vv) is used to evaluate cytokine-mediated T cell
function. Vaccinia virus replicates only in certain visceral mouse
organs, such as the ovaries or the brain, and is eliminated by
CD8+ and CD4+ effector T
cells via an IFN-
-dependent mechanism. Abs play no role in vv models
used (14).
Vesicular stomatitis virus (VSV) is used to assess humoral immune responses. Infection of mice with VSV leads to the rapid generation of neutralizing Abs. Within 4 days, a Th-independent IgM response is generated, followed by a strictly CD4+ Th-dependent IgG response (15).
While we conform an important role of fucosylated selectin ligands for trafficking of CD4+ and CD8+ T cells to the skin, we found that T cell extravasation in visceral organs is not impaired.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The generation of the FucTVII-/- mice has previously been described in detail (10). Founder mice were backcrossed into C57BL/6 mice for more than six generations. Mice were bred and kept under strict specified pathogen-free conditions at the Biologisches Zentrallabor of the University Hospital of Zürich.
Viruses
LCMV strain WE was originally obtained from F. Lehmann-Grube (Hamburg, Germany). The virus was propagated on BHK cells and plaqued on MC57 cells using an immunological focus assay, as described earlier (16). VSV serotype Indiana (Mudd-Summer isolate) was originally obtained from D. Kolakovsky (University of Geneva, Geneva, Switzerland). Seeds were grown on BHK cells and plaqued on Vero cells following standard protocols (17). The recombinant vv expressing VSV nucleoprotein (vv-VSV-np) was originally obtained from B. Moss (National Institutes of Health, Bethesda, MD) (18). Recombinant vv expressing VSV-gp (vv-VSV-gp) was a gift from D. Bishop (Oxford, U.K.).
In vivo protection assays for CD8+ and CD4+ T cell activity
The in vivo assays for the detection of CD8+ or CD4+ T cell activity by challenge infections with recombinant vv have been described in detail previously (14). To assess T cell-mediated antiviral protection in the ovaries, mice are immunized with VSV wt virus (2 x 106 PFU i.v.). After 10 days, mice are challenged i.v. with 2 x 106 PFU vv-VSV-np or vv-VSV-gp. Five days after the challenge infection, ovaries are removed and homogenized to measure vv titers. To measure T cell-mediated antiviral protection in the brain, mice are immunized with VSV wt virus (2 x 106 PFU i.v.). After 21 days, mice are challenged intracerebrally with 1 x 103 PFU vv-VSV-np or vv-VSV-gp. Three days after the challenge infection, brains are removed and homogenized to determine vv titers. The virus titers are determined using a standard virus plaque assay on bovine skin cells (19).
Measurement of primary ex vivo cytotoxicity against VSV and LCMV
Mice were infected i.v. with VSV (2 x 106 PFU). On day 6, mice were sacrificed and spleen cells were coincubated for 5 h with 51Cr-labeled target cells. EL-4N1 is a thymoma cell line originating from C57BL/6 mice that was transfected to express VSV-np. EL-4V1 is the control cell line transfected with the vector only (20). Both cell lines were obtained from L. Lefrancois (Connecticut Health Center, Farmington, CT). Mice infected with LCMV (5 x 102 PFU) i.v. were sacrificed on day 8, and spleen cells were coincubated for 5 h with EL-4 cells either unpulsed or pulsed with p33 (aa 33–42 of LCMV-gp). Specific lysis was calculated as [(experimental 51Cr release x spontaneous 51Cr release)/(total 51Cr release x spontaneous 51Cr release)] x 100%.
FITC-induced ear-swelling reaction
Mice were sensitized against FITC by painting the shaved abdomen with 0.4 ml 0.5% FITC (Sigma, St. Louis, MO) in acetone-dibutyl phthalate (1:1 v/v). After 6 days, the delayed-type hypersensitivity (DTH) was elicited by painting both sides of the ears with 0.5% FITC. After 24 h, the increase in ear thickness was measured using a spring-loaded caliper. Ear swelling is calculated as [(measured thickness - thickness before injection)/(thickness before injection)] x 100%.
LCMV-induced footpad-swelling reaction
Mice were infected with LCMV strain WE by injection into the hind footpad (500 PFU in 30 µl). Footpad thickness was measured daily using a spring-loaded caliper. Footpad swelling is calculated as [(measured thickness - thickness before injection)/(thickness before injection)] x 100%.
T cell proliferation assays
Mice were painted on both ears with 0.5% FITC in acetone-dibutyl phthalate (1:1 v/v). After 7 days, regional lymph nodes were removed and lymph node cells were restimulated in vitro by adding 0.005% FITC to the cultures. [3H]Thymidine was added to cultures after 48 h. [3H]Thymidine incorporation was assessed 12 h later.
Determination of neutralizing Ab titers against VSV
Mouse sera were prediluted 40-fold in supplemented MEM and then heat inactivated for 30 min at 56°C. Serial 2-fold dilutions were mixed with equal volumes of virus diluted to contain 500 PFU/ml. The mixture was incubated for 90 min at 37°C in an atmosphere with 5% CO2. Then 100 µl of the serum-virus mixture was transferred onto Vero cell monolayers in 96-well plates and incubated for 1 h at 37°C. The monolayers were then overlaid with 100 µl DMEM containing 1% methylcellulose. After incubation for 24 h at 37°C, the overlay was flicked off, and the monolayer was fixed and stained with 0.5% crystal violet. The highest dilution of serum that reduced the number of plaques by 50% was taken as the titer. Because of the addition of an equal volume of virus, the titer was considered to be one 2-fold dilution higher. To determine the IgG titers, undiluted serum was pretreated with an equal volume of 0.1 M 2-ME in saline for 1 h, which reduces the IgM exclusively (21). The neutralizing capacity of unreduced samples was interpreted as IgM titers only if the corresponding reduced samples had at least a 4-fold lower titer, i.e., when the IgG present in the unreduced sample could be neglected.
Analysis of Langerhans cell (LC) migration
Ears were painted on both sides with 0.5% FITC dissolved in
acetone-dibutyl phthalate (1:1 v/v). After 24 h, single cell
suspensions of regional neck lymph node cells were prepared. A
metrizamide gradient was used to enrich for DCs. A total of 1 x
106 such enriched cells was stained with
PE-labeled anti-CD11c Ab by incubating for 30 min at 4°C in the
dark (clone HL3 hamster IgG, group 1, 
, against integrin
x-chain; PharMingen, San Diego, CA). Cells
were subsequently washed with PBS containing 2% FCS and 0.01% sodium
azide and then fixed in 1% formaldehyde. Samples were analyzed using a
FACSCalibur flow cytometer (Becton Dickinson, San Jose, CA). The
appropriate isotype-matched Ab (PE hamster IgG, group 1, isotype
standard anti-trinitrophenyl; PharMingen) was used to control
for specific staining.
Adoptive transfer experiments
A total of 4 x 106 T cells isolated from spleens of FucTVII-/- and FucTVII+/+ donor mice was adoptively transferred by tail vain injection into FucTVII-/- and FucTVII+/+ recipient mice, respectively. After 24 h, recipient mice were sensitized by painting their ears with 0.5% FITC in acetone-dibutyl phthalate (1:1 v/v). Seven days after sensitization, the contact hypersensitivity reaction was elicited by painting ears with 0.5% FITC in acetone-dibutyl phthalate (1:1 v/v) again. The ear swelling was measured 24 h after eliciting the reaction.
Tumor challenge experiments
The generation of EL-4N1 cells has been described in detail previously (20). The tumor model has been described in detail previously (22). Briefly, mice were immunized i.v. with 2 x 106 PFU of VSV wt, and after 14 days challenged i.v. with 1 x 103 EL-4N1 cells. Lethally sick mice were sacrificed, and tumor growth was assessed by macroscopic inspection.
Immunohistochemistry
Freshly removed organs were immersed in PBS and snap frozen in liquid nitrogen. Tissue sections of 5 µm thickness were cut and fixed in acetone for 10 min. Sections were then incubated with primary Ab for 30 min at room temperature. Abs used included anti-CD8 (mAb YTS169) and anti-CD4 (mAb YTS191). Primary Abs were followed by a two-step indirect immunoenzymatic staining procedure. First, alkaline phosphatase-labeled goat Abs to rat Ig were applied for 30 min. Alkaline phosphatase was then detected by a red color reaction using naphtho-AS-BI phosphate and New Fuchsin as substrate. Endogenous alkaline phosphatase was blocked by Levamisol. Sections were counterstained with Mayer’s hemalum for 2 min.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The DTH reaction against the contact-sensitizing agent FITC is
mediated by Th2-type CD4+ T cells
(23). In FucTVII-/- mice, the
ear-swelling reaction was significantly reduced (Fig. 1
A).
|
, B and C). However, from day 10–15,
FucTVII-/- mice exhibited an enhanced swelling
reaction, possibly representing delayed virus elimination (Fig. 1B). Immunohistochemical analysis of the swelling reaction
on day 14 showed a dense cellular infiltration with
CD8+ and CD4+ T cells as
well as histiocytes. The composition of the infiltrate was not
significantly different in FucTVII-/- and
FucTVII+/+ mice (data not shown). The above DTH reactions involve a series of events. To determine which step is impaired in FucTVII-/- mice, LC migration, T cell induction, or T cell extravasation into the skin was assessed separately.
LC migration into regional lymph nodes is not impaired in FucTVII-/- mice
FITC is a contact sensitizer that, after being painted onto the
skin, is picked up by LC. These are activated to leave the epidermis
and migrate into the draining lymph node, where FITC-stained LC can be
found 24 h later. In both FucTVII+/+ (Fig. 2A) and
FucTVII-/- (Fig. 2B) mice, a similar
proportion of CD11c-positive LC in the lymph node was labeled
with FITC, demonstrating that LC migration was not impaired in
FucTVII-/- mice.
|
T cell induction by FITC in the regional lymph nodes was monitored
by proliferation assays. FITC was painted onto the ears, and 7 days
later the regional lymph nodes were removed. In vitro restimulation
with FITC revealed similar proliferation of T cells in lymph nodes of
FucTVII-/- and FucTVII+/+
mice (Fig. 3A).
|
B).
We also evaluated the generation of CD8+ T cells
in spleens of LCMV- and VSV-infected mice.
FucTVII-/- and FucTVII+/+
mice generated comparable antiviral CTL activity 8 and 6 days after
i.v. LCMV (Fig. 3C) and i.v. VSV (Fig. 3D)
infection, respectively.
Adoptive transfer of FucTVII+/+ T cells restores cutaneous hypersensitivity
FucTVII+/+ and
FucTVII-/- T cells were adoptively
transferred into FucTVII+/+ and
FucTVII-/- mice. Reconstitution of
FucTVII-/- mice with
FucTVII+/+ T cells restored cutaneous
hypersensitivity to FITC (Fig. 4). This
confirms that the absence of cutaneous hypersensitivity in
FucTVII-/- mice was due to a defect in the
effector arm of the response.
|
The reduced DTH observed in FucTVII-/- mice was apparently due to impaired T cell extravasation into the skin, whereas the afferent arm of the DTH, i.e., LC migration into the regional lymph nodes and T cell induction in lymphoid organs, was not impaired. The following in vivo antiviral protection assays shall evaluate T cell extravasation into visceral organs, such as the ovaries or the brain.
In H-2b mice, infection with VSV wt induces a CD8+ T cell response against the nucleoprotein of the virus, but not against the glycoprotein. In contrast, the CD4+ T cell responses are directed against the glycoprotein, but not against the nucleoprotein (24). Thus, if VSV-immunized H-2b mice are challenged with vv-VSV-np, only the CD8+ T cells can protect against the recombinant virus. In contrast, if mice are challenged with vv-VSV-gp, then only CD4+ T cells can protect against the recombinant virus. Since recombinant vv do not incorporate VSV proteins into their membranes, Abs play no role in protection (14, 24).
Mice were immunized i.v. with VSV wt, and 10 days later i.v. challenged
with vv-VSV-gp. After another 5 days, ovaries were removed to determine
titers of vv-VSV-gp. In both FucTVII+/+ mice and
FucTVII-/- mice, immunization with VSV led to a
similar reduction in vv-VSV-gp titers, demonstrating comparable
protection by VSV-gp-specific CD4+ T cells (Fig. 5A). Such protection involves
rapid CD4+ T cell extravasation and infiltration
into ovary tissue. Similarly, mice were immunized i.v. with VSV wt, and
21 days later intracerebrally challenged with vv-VSV-gp. After 3 days,
the brains were removed to determine vv-VSV-gp titers. By then, both
FucTVII+/+ and FucTVII-/-
mice had eliminated vv-VSV-gp below detection limits, demonstrating
rapid and efficient extravasation of VSV-gp-specific
CD4+ T cells into the brain (Fig. 5C).
|
B) and brains (Fig. 5D) was
comparable in FucTVII-/- and
FucTVII+/+ mice, suggesting that
CD8+ T cell extravasation into these visceral
organs was not impaired.
CD8+ T cell extravasation into skin and visceral
organs was also assessed by immunohistochemistry. Mice were infected
with LCMV via footpad injection. After 7 days, i.e., 1 day before the
immunopathological swelling reaction peaks, mice were sacrificed. The
footpad skin of FucTVII+/+ mice was infiltrated
by CD8+ T cells (Fig. 6, A and C). In
contrast, FucTVII-/- mice showed no
infiltration with CD8+ T cells (Fig. 6, B and C).
|
, D, F,
G, and I) and FucTVII-/-
mice (Fig. 6, E, F, H, and
I) showed comparable infiltration of ovary tissue and brain
tissue with CD8+ T cells. Protection against lethal choriomeningitis is not impaired in FucTVII-/- mice
The above assessed protection against recombinant vv depends on
cytokine-mediated CD4- or
CD8- T cell function. The following experiments
are designed to measure perforin-dependent CD8-mediated antiviral
protection. Mice were immunized i.v. with vv-LCMV-gp to induce
LCMV-gp-specific CD8+ T cells. These T cells then
protect the mouse from lethal choriomeningitis after intracerebral
challenge infection with LCMV wt via a perforin-dependent mechanism. It
should be noted that stringent conditions were chosen for this assay to
detect even minor defects of CD8+ T cell
extravasation: immunization with vv-LCMV-gp induces merely weak
CD8+ T cell responses, whereas protection against
intracerebral challenge infection with LCMV wt virus requires
relatively strong CD8+ T cell memory
(25). Not surprisingly, only approximately 50% of the
FucTVII+/+ mice survived such challenge infection
(Table I). In
FucTVII-/- mice, however, comparable numbers of
mice survived.
|
EL-4, a thymoma originating from C57BL/6 mice, is a highly
aggressive tumor. We have previously established a tumor model in which
VSV infection generates a VSV-np-specific CD8+ T
cell response protecting mice against a tumor challenge with EL-4 cells
transfected with VSV-np (EL-4N1) (20, 22). Mice were
either immunized with VSV wt or left unprimed. Fourteen days later, all
mice were challenged i.v. with EL-4N1 cells. Within 24 days, all naive
control mice succumbed to lethal tumor growth in several major visceral
organs, such as in the liver, lung, spleen, and peritoneum
(Table II). In contrast, both VSV wt
immunized FucTVII+/+ and VSV wt
immunized FucTVII-/- mice survived. This
suggested that FucTVII-/- mice showed efficient
CD8+ T cell extravasation into all major visceral
organs.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The data presented in this study confirm the absence of cutaneous hypersensitivity to FITC in FucTVII-/- mice, a reaction mediated by CD4+ T cells mainly of the Th2 type (23). Also, CD8+ T cell-mediated DTH against LCMV infection of the skin was found to have a slower kinetics in FucTVII-/- mice. Whereas FucTVII+/+ animals already showed significant footpad swelling 7 days after infection and corresponding infiltration with CD8+ T cells, no swelling reaction and no CD8+ T cell infiltration could be seen in footpads of FucTVII-/- mice by day 7. In these mice, the swelling reaction was reproducibly delayed by 24 h. While the peak of the reaction around day 8 was reduced in FucTVII-/- mice, the later phase of the swelling reaction around day 10–15 was enhanced, consistent with delayed virus elimination. At this later time point, there was a dense cellular infiltration of the footpads consisting of CD8+ and CD4+ T cells, as well as histiocytes. This infiltrate was comparable between FucTVII-/- and FucTVII+/+ mice. Thus, the LCMV model demonstrates a significant delay of CD8+ and CD4+ T cell extravasation into the skin, but not a complete absence. This observation would be consistent with the hypothesis that fucosyltransferase IV may direct a low degree of residual E- and P-selectin ligand expression by activated T cells (11), similar to the situation in neutrophils (27).
We analyzed the afferent arm of the DTH response. LC migration into the draining lymph nodes was not impaired in FucTVII-/- mice, despite the fact that LC express the sialyl Lewis x determinant and the cutaneous lymphocyte Ag (CLA), which both depend on fucosylation (28, 29). We also demonstrate normal induction and generation of specific CD8+ and CD4+ T cell responses specific for VSV, LCMV, and VSV in draining lymph nodes and spleens. Thus, the observation that lymph nodes of FucTVII-/- mice show a reduction of CD8+ and CD4+ T cell numbers of 50% (11) has no impact on the generation of the T cell response.
We confirmed by adoptive transfer experiments that the reduction of T cell-mediated DTH in FucTVII-/- mice was exclusively due to impaired extravasation of effector T cells into skin: reconstitution of FucTVII-/- mice with FucTVII+/+ T cells fully restored the cutaneous hypersensitivity response.
Interestingly, analysis using the same viral model systems revealed
functionally normal CD8+ and
CD4+ T cell extravasation into visceral organs
such as the ovaries and the brain. The assay conditions were chosen
most stringently, to detect even minor defects or delays in
extravasation. In the experiments assessing CD8+
and CD4+ T cell extravasation into ovaries, the
latter organs were removed as soon as 3 days after challenge infection,
i.e., at a time point in which vv is not completely eliminated (Fig. 5). Also, when CD8+ T cell-mediated protection
against intracerebral LCMV challenge infection was assayed, mice were
immunized only with vv-LCMV-gp, which induces relatively weak
CD8+ T cell responses, able to protect only 50%
of wt mice. Again, these stringent conditions should reveal even minor
extravasation defects of CD8+ T cells in
FucTVII-/- mice. However, the degree of
protection in FucTVII-/- and
FucTVII+/+ mice was comparable in all viral
challenge assays. In accordance with functionally efficient
CD4+ and CD8+ T cell
extravasation into the brain and ovaries, immunohistochemical analysis
as early as 24 h after challenge infection showed comparable organ
infiltration with CD8+ and
CD4+ T cell FucTVII-/-
and FucTVII+/+ mice. Additional tumor challenge
experiments showed that CD8+ T cell mediated
protection against metastasis in several other visceral organs of
FucTVII-/- mice, suggesting that the results on
T cell extravasation into brains and ovaries may be representative for
visceral organs in general. Thus, the results suggest that interactions
between selectins and their ligands may be more important for T cell
homing to the skin than for T cell homing to visceral organs.
Most of our findings in the FucTVII-/- mice are consistent with the immune defects reported in E-selectin and P-selectin double-deficient mice (E/P-/-), which show enhanced susceptibility to cutaneous bacterial infection (30, 31) and reduced migration of CD4+ T cells into skin (32, 33, 34, 35), whereas leukocyte migration into inflamed liver and CD4+ T cell migration into the brain using an experimental autoimmune encephalomyelitis model were found to be normal (31, 36). Few studies, however, also report impaired leukocyte extravasation into visceral organs (30, 37).
Interestingly, our findings differ from those reported in a recent study using the LCMV system to analyze CD8+ T cell function and extravasation in E/P-selectin-/- mice, in which the LCMV-induced footpad swelling was found to be normal (38). Since the FucTVII-/- mice lack functional E-, P-, and L-selectin ligands, this difference points toward a role of L-selectin ligands, especially in lymphocyte extravasation into the skin. The importance of L-selectin in mediating leukocyte migration into the skin has been demonstrated using models of contact hypersensitivity and allogeneic skin transplantation (39, 40). The specificity of the defect for skin homing could be explained by the recent finding, that the CLA displayed on PSGL-1 on leukocytes is a predominant L-selectin ligand (41). CLA is expressed by neutrophils, monocyte subsets, a small fraction of leukocytes in lymph nodes, and endothelium at sites of chronic inflammation. Most notably, CLA has been characterized as a specialized carbohydrated form of PSGL-1 (42), which is specifically expressed on skin-homing T cells (42, 43, 44, 45). PSGL-1 displays sialyl Lewis x-like carbohydrate determinants, which require fucosylation with FucTVII (46), and has recently been identified as the predominant ligand for L-selectin expressed on vascular endothelium (41).
In conclusion, the emphasis of this study was on functional in vivo analysis of T cell trafficking to the skin and several visceral organs by the use of viral model systems and a tumor model system. We could confirm that selectin ligands play an important role in T cell extravasation into the skin. However, analysis of T cell trafficking to visceral organs showed no significant role for selectin ligands.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Thomas M. Kündig, Department of Dermatology, University Hospital Zürich, Gloriastr. 31, 8091 Zürich, Switzerland. E-mail address: tkuendig{at}derm.unizh.ch
3 Abbreviations used in this paper: PSGL-1, P-selectin glycoprotein ligand-1; CLA, cutaneous lymphocyte-associated Ag; DTH, delayed-type hypersensitivity; FucTVII, -1,3-fucosyltransferase VII; LC, Langerhans cell; LCMV, lymphocytic choriomeningitis virus; np, nucleoprotein; VSV, vesicular stomatitis virus; vv, vaccinia virus; wt, wild type.
Received for publication January 29, 2001. Accepted for publication January 4, 2002.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-L-fucosyltransferase of LEC11 and LEC12 Chinese hamster ovary mutants exhibit novel specificities for glycolipid substrates. J. Biol. Chem. 262:1683.
(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis. Cell 86:643.[Medline]
(1, 3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels. Immunity 12:665.[Medline]
(1, 3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing. Immunity 15:115.[Medline]
This article has been cited by other articles:
|
|
 |
|
  C. Doebis, K. Siegmund, C. Loddenkemper, J. B. Lowe, A. C. Issekutz, A. Hamann, J. Huehn, and U. Syrbe Cellular Players and Role of Selectin Ligands in Leukocyte Recruitment in a T-Cell-Initiated Delayed-Type Hypersensitivity Reaction Am. J. Pathol., October 1, 2008; 173(4): 1067 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Dudda, N. Perdue, E. Bachtanian, and D. J. Campbell Foxp3+ regulatory T cells maintain immune homeostasis in the skin J. Exp. Med., July 7, 2008; 205(7): 1559 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rana, S. N. Byrne, L. J. MacDonald, C. Y.-Y. Chan, and G. M. Halliday Ultraviolet B Suppresses Immunity by Inhibiting Effector and Memory T Cells Am. J. Pathol., April 1, 2008; 172(4): 993 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ou, M. Zhang, L. Huang, R. A. Flavell, P. A. Koni, and D. Moskophidis Regulation of Immune Response and Inflammatory Reactions against Viral Infection by VCAM-1 J. Virol., March 15, 2008; 82(6): 2952 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jennrich, B. A. Ratsch, A. Hamann, and U. Syrbe Long-Term Commitment to Inflammation-Seeking Homing in CD4+ Effector Cells J. Immunol., June 15, 2007; 178(12): 8073 - 8080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Allahverdian, K. R. Wojcik, and D. R. Dorscheid Airway epithelial wound repair: role of carbohydrate sialyl Lewisx Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L828 - L836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Biedermann, G. Lametschwandtner, K. Tangemann, J. Kund, S. Hinteregger, N. Carballido-Perrig, A. Rot, C. Schwarzler, and J. M. Carballido IL-12 Instructs Skin Homing of Human Th2 Cells J. Immunol., September 15, 2006; 177(6): 3763 - 3770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Cai, A. Alvarez, P. Alcaide, P. Duramad, Y.-C. Lim, P. Jarolim, J. B. Lowe, F. W. Luscinskas, and A. H. Lichtman Abrogation of Functional Selectin-Ligand Expression Reduces Migration of Pathogenic CD8+ T Cells into Heart. J. Immunol., June 1, 2006; 176(11): 6568 - 6575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schreiber, S. Ehlers, S. Aly, A. Holscher, S. Hartmann, M. Lipp, J. B. Lowe, and C. Holscher Selectin Ligand-Independent Priming and Maintenance of T Cell Immunity during Airborne Tuberculosis J. Immunol., January 15, 2006; 176(2): 1131 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schachter The search for glycan function: Fucosylation of the TGF-{beta}1 receptor is required for receptor activation PNAS, November 1, 2005; 102(44): 15721 - 15722. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Siegmund, M. Feuerer, C. Siewert, S. Ghani, U. Haubold, A. Dankof, V. Krenn, M. P. Schon, A. Scheffold, J. B. Lowe, et al. Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo Blood, November 1, 2005; 106(9): 3097 - 3104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Masopust, V. Vezys, E. J. Usherwood, L. S. Cauley, S. Olson, A. L. Marzo, R. L. Ward, D. L. Woodland, and L. Lefrancois Activated Primary and Memory CD8 T Cells Migrate to Nonlymphoid Tissues Regardless of Site of Activation or Tissue of Origin J. Immunol., April 15, 2004; 172(8): 4875 - 4882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hiraiwa, T. Yabuta, K. Yoritomi, M. Hiraiwa, Y. Tanaka, T. Suzuki, M. Yoshida, and R. Kannagi Transactivation of the fucosyltransferase VII gene by human T-cell leukemia virus type 1 Tax through a variant cAMP-responsive element Blood, May 1, 2003; 101(9): 3615 - 3621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Reinhardt, D. C. Bullard, C. T. Weaver, and M. K. Jenkins Preferential Accumulation of Antigen-specific Effector CD4 T Cells at an Antigen Injection Site Involves CD62E-dependent Migration but Not Local Proliferation J. Exp. Med., March 17, 2003; 197(6): 751 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Dimitroff, R. J. Bernacki, and R. Sackstein Glycosylation-dependent inhibition of cutaneous lymphocyte-associated antigen expression: implications in modulating lymphocyte migration to skin Blood, January 15, 2003; 101(2): 602 - 610. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) and FucTVII-/- (
) mice
were injected into hind footpads with 500 PFU LCMV WE. Subsequent
footpad swelling was measured daily. C, Another group of
FucTVII+/+ (
) mice
were immunized i.v. with VSV wt. Neutralizing serum IgM titers were
determined on day 4. Neutralizing IgG titers were measured on days 8,
12, and 20 after immunization. C,
FucTVII+/+ (
and 
). Primary ex vivo cytotoxicity was
assessed by 51Cr release assays on syngenic EL-4 target
cells pulsed with p33 (•, 
