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RI-Dependent Mast Cell Degranulation Following Coculture with Activated T Cells: Dependency on ICAM-1- and Leukocyte Function-Associated Antigen (LFA)-1-Mediated Heterotypic Aggregation
*
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Fujisawa Pharmaceutical Co., Ibaraki, Japan; and
Department of Medicine, Meir General Hospital, Kfar-Saba, and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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RI cross-linking-induced degranulation
was augmented when BMCMC were cocultured with activated T cells.
Supernatants of activated T cells failed to exert the stimulatory
effect. Separation of the two cell populations with a porous membrane
prevented degranulation, indicating that BMCMC activation was adhesion
dependent. Indeed, the kinetics of histamine release paralleled the
kinetics of the formation of heterotypic aggregates, which peaked after
12 h of coculture. Introduction of anti-LFA-1 and
anti-intercellular adhesion molecule-1 mAb inhibited the
adhesion-induced mast cell degranulation. These data suggest a
heretofore unrecognized mast cell activation pathway induced by
LFA-1/intercellular adhesion molecule-1-mediated heterotypic
aggregation with activated T cells. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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To date, the inductive effects of T cells on mast cell activation and
degranulation have been attributed to the biologic effects of cytokines
released from the former. Cytokines have been shown to affect mast cell
degranulation by two different mechanisms. First, several cytokines
such as IL-1, IL-3, and MIP-1
were found to directly induce mast
cell degranulation (15, 16, 17). Second, by priming mast cells, cytokines
may potentiate the effect of, and thus operate synergistically with,
"classical" secretagogues such as Ag, anti-IgE Abs, or
complement components (15). These studies, however, have not examined
the possibility that activated lymphocytes might be able to directly
affect mast cells through cell-to-cell contact in the absence of
demonstrable soluble inflammatory mediators.
To examine this hypothesis, we chose to determine whether
activated lymphocytes, through cell-to-cell interaction, could induce
or enhance mast cell degranulation. As will be shown, activated
lymphocytes aggregated with resting mast cells. This aggregation was
accompanied by enhanced FcRI-dependent histamine release. Moreover,
heterotypic aggregation with activated T cells not only enhanced but
also directly induced degranulation of mast cells; however, unlike in
previous reports, this effect was not mediated by soluble factor(s) but
by direct contact through certain adhesion molecules between these two
cell populations. Thus, histamine release did not occur in the absence
of heterotypic aggregation, suggesting a novel, heretofore-undescribed
mechanism of mast cell activation by direct contact with activated T
lymphocytes.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Mouse IgE mAb specific for DNP, DNP-human serum albumin
(HSA),2 PMA, BSA, 2-ME,
citric acid, and glycine (Sigma Chemical, St. Louis, MO); hamster
anti-mouse CD3 mAb, hamster anti-mouse CD5 mAb, hamster IgG,
rat anti-mouse LFA-1 chain (CD11a) mAb, rat anti-mouse
LFA-1ß chain (CD18) mAb, hamster anti-mouse CD54 (intercellular
adhesion molecule-1 (ICAM-1)) mAb, rat anti-mouse CD49d (4
integrin) mAb, rat anti-mouse vascular cell adhesion molecule-1
(INCAM-110) mAb, rat IgG2a6 (PharMingen, San Diego, CA); goat
anti-rat IgG (H+L), goat anti-hamster IgG (H+L), FITC conjugate
(Caltag, South San Francisco, CA); RPMI 1640 medium, FCS, sodium
pyruvate, nonessential amino acids, L-glutamine, HEPES, and
penicillin/streptomycin (Biofluids, Inc., Rockville, MD); and 96-well
microtiter plates (Costar, Cambridge, MA) were purchased from the
manufacturers.
Cell cultures
Murine bone marrow-derived cultured mast cells (BMCMC) were cultured from bone marrow obtained from the femurs of BALB/c mice. Cells were maintained in RPMI 1640 supplemented with 10% heat-inactivated FCS, 10% (v/v) WEHI-3 supernatant as a source of IL-3, 25 mM HEPES, 4 mM L-glutamine, 100 µg/ml penicillin/streptomycin, 0.1 mM nonessential amino acids, and 1 mM sodium pyruvate (complete RPMI) at 37°C in a CO2 incubator as described (18). Cell cultures were centrifuged at 400 x g weekly and the cell pellets resuspended in fresh media. After 4 to 5 wk in culture, the mast cell number was assessed by acid toluidine blue staining and cell viability determined by trypan blue dye exclusion. BMCMC used in experiments consisted of greater than 97% mast cells and were of 98% or greater viability.
EL-4 cells and T cell hybridoma 2B4 cells were cultured in RPMI 1640 supplemented with 10% FCS, 25 mM HEPES, 4 mM L-glutamine, 100 µg/ml penicillin/streptomycin, 0.1 mM nonessential amino acids, and 1 mM sodium pyruvate. Freshly isolated T cells were obtained from BALB/c mice spleens using the IsoCell T cell isolation kit (Pierce, Rockford, IL).
Stimulation of cells
Activation of T cells was conducted by incubating 2B4 cells with immobilized anti-CD3 Ab. Briefly, individual wells of 96-well plates were first incubated with 25 µg/ml of anti-CD3 mAb or with the hamster IgG isotype control for 16 h at 4°C. At the end of incubation, wells were washed and 2B4 cells were added at a concentration of 1 x 105 cells/well and incubated for 15 min before the addition of BMCMC.
Mast cells were sensitized with IgE anti-DNP mAb by incubating 1 x 106 BMCMC with 1 µg of the Ab (2 h; 4°C). Cells were washed twice in RPMI 1640 and cocultured with 2B4 cells at a 1:1 ratio with a total of 2 x 105 cells/well. Stimulation of mast cells was conducted by the addition of DNP-HSA followed by detection of histamine release in the supernatants after 30 min.
Histamine assay
Culture supernatants were collected and the histamine content determined using an ELISA (Immunotech, Westbrook, ME) per the manufacturer’s instructions. Histamine concentrations (nM) were calculated from the standard curve, and percentage release of histamine was calculated as follows: % histamine release = 100 x S/T, where S is histamine concentrations in supernatants obtained from the cocultures and T is the total histamine concentration in BMCMC lysates disrupted by 1.2% Triton X-100. Histamine release data is compared using Student’s paired sample t test (two-tailed).
FACS analysis
Cells were adjusted to 1 x 106 cells/ml PBS containing 0.05% NaN3 and 0.1% BSA and incubated with 10 µg/ml of specific anti-adhesion molecule Abs for 30 min on ice. After washing three times, cells were incubated with a 1:200 dilution of a secondary Ab conjugated to FITC directed against the isotype of the primary Ab for 30 min on ice in the dark. The cells were washed three times and resuspended in 500 µl of sorter buffer. Cell staining was analyzed with a FACScan (Becton Dickinson, Mountain View, CA). The percentage of specifically labeled cells was determined by setting a fluorescence threshold using the appropriate isotype control histogram for subtracting the signal generated by the control Ab.
Quantitation of cell aggregation
BMCMC and 2B4 cells were cocultured at a 1:1 ratio at a concentration of 2 x 105 cells/well and incubated for the periods indicated. Aggregate formation was quantitated by phase-contrast microscopy using a calibrated ocular grid as described previously (19). The percentage of cells forming aggregates was determined by counting free cells within the grid in six randomly selected grids within one well and then applying the following equation: % aggregation = (1 - no. of free cells/no. of total cells) x 100.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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It has previously been proposed that T cell-derived soluble
mediators might affect mast cell function (15, 16, 17); however, whether
lymphocytes are able to induce mast cell activation/degranulation
through a mechanism requiring cell-to-cell contact has not yet been
fully elucidated. To initially explore this question, we first analyzed
the effect of mitogen or Ag-induced T cell activation on mediator
release by mast cells. Thus, EL-4 cells were preincubated for 30 min in
the presence or absence of PMA (50 ng/ml), washed three times, and then
cocultured with sensitized BMCMC for 16 h. At the end of
incubation, Ag (DNP-HSA; 10 ng/ml) was added to some of the cocultures,
and histamine release was measured at 30 min. As shown in Figure 1
, nonactivated T cells induced only a
mild increase in histamine release from either resting or activated
mast cells; however, PMA-activated EL-4 cells augmented histamine
release from sensitized mast cells both with and without Ag
cross-linking of the FcRI (47% and sixfold increase when compared
with BMCMC alone, respectively). When BMCMC were treated with PMA
alone, i.e., without the presence of T cells, no enhancement of
degranulation could be detected (not shown). A similar mitogenic
stimulation of the T cell hybridoma 2B4 also induced a significant
augmentation of histamine release from both resting or Ag-stimulated
sensitized mast cells (not shown).
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A, 2B4 cells
that were preincubated with the immobilized hamster IgG isotype control
did not have any noticeable effect on histamine release when compared
with background release by resting mast cells. Activation of 2B4 cells
with anti-CD3, however, induced a significant increase in histamine
release from the cocultured mast cells (29 ± 1.9%) compared with
either resting, nontreated mast cells (BMCMC alone) or with mast cells
cocultured with nonstimulated T cells (6 and 8% histamine release,
respectively). When EL-4 cells, which are known to express only low
levels of CD3, were incubated with BMCMC in the presence of immobilized
anti-CD3, no significant histamine release was detected (10 ±
2% vs 7.5 ± 1.5% of BMCMC alone, not shown). This finding
indicates that in this system, cell activation via CD3 is necessary for
T cell-induced histamine release by mast cells. As with hybridoma T
cells, active, but not resting, freshly isolated T cells induced
histamine release from BMCMC (Fig. 2B). As can also
be seen in Figure 2B, anti-CD5 Ab-treated T cells did
not induce degranulation of mast cells, indicating once again that T
cell-induced mast cell activation is mediated via CD3.
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RI
cross-linking to augment histamine release from mast cells. Thus, as
shown in Figure 3, histamine release that
ensued upon activation of sensitized mast cells with the specific Ag
was significantly augmented only when mast cells were cocultured with
activated 2B4 cells. This effect was most remarkable at suboptimal
concentrations of Ag (1 ng/ml). Mast cells were never found to
degranulate after incubation on plates coated with immobilized
anti-CD3 mAb, thus confirming previous observations (21). It
therefore may be concluded that T cell activation results in a
significant induction and/or augmentation of mast cell
degranulation.
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Mast cells have been reported to be in close apposition with
activated T cells in various inflammatory conditions (1, 2, 3, 4, 5, 6, 7). Moreover,
electron microscopic studies of inflamed allergic tissues have
documented apparent interdigitations of lymphocytes and mast cell
membranes (8). We therefore determined, in the next set of experiments,
whether a cell-to-cell contact between T cells and mast cells is
required for the induction of histamine release. For this purpose, we
first analyzed the kinetics of histamine release induced by
anti-CD3-activated T cells. Thus, 2B4 cells were preincubated for
15 min in wells precoated with either anti-CD3 mAb or with the
isotype IgG control Ab. BMCMC were then added for an incubation period
that lasted for 24 h. Sample supernatants were collected at
several time points for the measurement of histamine release. As shown
in Figure 4, histamine release was first
detected at 8 h, with maximal release at 16 to 24 h. Once
again, an enhanced release was detected only in cocultures that
included activated 2B4 cells. Cultures in which BMCMC were incubated
alone or with nonactivated 2B4 cells did not show increased histamine
in the supernatant.
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). At 1 and
4 h of incubation, 2B4 cells incubated alone or with IgG or with
bound anti-CD3 showed minimal aggregation with BMCMC. Percent of
aggregation significantly increased at 8 h of coculture.
Microscopic examination of cell aggregates confirmed they were
heterotypic in nature. As patterns shown in Figures 4
and 5 were quite
similar, it appeared that lymphocyte-mast cell aggregation was related
to mast cell histamine release.
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Two different experimental approaches were employed to further
elucidate the role of intercellular contacts between T cells and mast
cells in the induction of histamine release. First, we used the
Transwell cell culture chamber (Costar) in which the two cell
populations were separated by a microporous membrane. As shown in
Figure 6, anti-CD3-activated 2B4
cells did not augment histamine release from BMCMC if these two cell
populations were separated by the Transwell chamber. Second,
supernatants from either resting or activated 2B4 cells, treated with
immobilized IgG or anti-CD3, respectively, were added to cultures
of BMCMC at 50% (v/v) and incubated for 16 h (Fig. 7). Supernatants of activated 2B4 cells
did not induce histamine release from BMCMC above that seen with
supernatants from 2B4 cells cultured alone or with IgG. These results
were consistent with the conclusion that cell-to-cell contact was
essential to promote histamine release induced by activated 2B4 cells
cocultured with mast cells.
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The expression and interaction between adhesion molecules is
essential for intercellular contacts. For example, for complete T cell
activation, the APC must provide additional costimulatory signals (22).
Besides secreting cytokines, the APC is obligated to give a
contact-dependent costimulatory signal, which is provided by molecules
present principally on the surface of activated APC (23, 24). Almost
all of these molecules proven to act in costimulation are also
considered to be involved in adhesion (25). Thus, the interaction of
LFA-1 (CD11/CD18) with its ligand ICAM-1 is required for
Ag-specific stimulation of T cells by eosinophils and some other
facultative APCs (26). Costimulation in these instances can be provided
by ICAM-1 on the APC binding the CD11/CD18 on the T cell or,
conversely, with ICAM-1 on the T cell binding CD11/CD18 on the APC. In
light of these observations, we first examined the expression of
adhesion molecules by T cells and mast cells using immunofluorescent Ab
labeling and flow cytometry. Mean mast cell purity in these experiments
was >97%. Flow cytometric analysis revealed that 31 ± 2.4%
BMCMC expressed ICAM-1, while LFA-1 (CD11) was found to be expressed
by only 4.5% of these cells. Also, 64.8% of mast cells were found to
express very late Ag (VLA)-4. On the other hand, virtually all 2B4
cells expressed CD11 (99.8 ± 2%), but only 3.7 and 4.3%
expressed ICAM-1 or VLA-4, respectively. Based on these initial
findings, CD11/CD18 and ICAM-1 were chosen as candidates for mediation
of heterotypic aggregation between BMCMC and 2B4 cells.
For the analysis of a possible role of adhesion molecules in our system
of heterotypic aggregation-induced mast cell activation, 2B4 cells were
preincubated for 10 min with 25 µg/ml of anti-CD11 mAb together
with anti-LFA-1ß (CD18), or with rat IgG2a isotype control Ab
before coculture. BMCMC with or without prior exposure (10 min) to
anti-ICAM-1 Ab or the isotype control were then added and
cocultured for 10 h, a time point at which a significant
augmentation of histamine release has been observed (Fig. 4).
Neutralizing Abs were present for the whole incubation period. As shown
in Figure 8, activated 2B4 cells induced
12% histamine release from the BMCMC, an effect that was significantly
inhibited by these Abs (4 ± 0.2% histamine release;
p < 0.02). As is also shown, isotype Abs did not
affect histamine release. When each of the anti-adhesion molecule
Abs was examined separately, no significant inhibition of histamine
release could be observed (data not shown). These data suggest that
heterotypic aggregation between T cells and mast cells is mediated at
least in part by CD11/CD18-ICAM-1 interactions that lead to stimulation
of the latter and histamine release.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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) or
anti-CD3-activated T cells (Fig. 2). Moreover, the intercellular
interaction between BMCMC and activated (but not resting) T cells used
in our system resulted in augmentation of Ag-FcRI
cross-linking-induced histamine release from mast cells (Fig. 3). As
noted above, soluble mediators might be the means by which activated T
cells activate mast cells (15, 16). Therefore, two different
experimental approaches were used to identify the nature of the
intercellular interaction observed in our study. First, separation
between T cells and mast cells by a porous membrane prevented the
ability of the former to activate the latter (Fig. 6). Second,
supernatants of activated 2B4 cells did not induce histamine release
after an incubation period that lasted 16 h (Fig. 7). These
observations indicate that soluble factors were not involved in the
induction of histamine release by activated 2B4 cells. Furthermore, the
kinetics of histamine release observed in this study (Fig. 4) are
different from those observed for cytokine-mediated release. While
release in our system was noticed only after 8 h of coculture,
cytokines are reported to induce histamine release during the first
hour after incubation with mast cells (16). Also, as shown in Figure 5, the kinetics of activated T cell-induced histamine release paralleled
the kinetics of the formation of heterotypic cell aggregates. Taken
together, these findings indicate that histamine release resulted from
heterotypic adhesion-induced activation of mast cells.
In analyzing the nature of the intercellular contacts observed in this
study, we first examined the expression of adhesion molecules known to
take part in such interactions. The integrin CD11 was constitutively
expressed on virtually all 2B4 cells, while 31% of the BMCMC expressed
ICAM-1 and 65% expressed VLA-4. Only 4.5% of the BMCMC expressed
CD11. This finding is in agreement with previous studies reporting the
expression of ICAM-1 and lack of expression of CD11 by murine
peritoneal mast cells (29). Also, human uterine mast cells were found
to express ICAM-1 and VLA-4 but were negative for CD11 (31). The cell
interaction receptor CD11/CD18, expressed by both human and murine
lymphocytes, interacts with ICAM-1 molecules. It is now well
established that this specific interaction between the integrin and its
ligand is essential for the activation of T cells by other cells such
as APC and for leukocyte transmigration (reviewed in 32 . For
complete T cell activation leading to proliferation, the APC has to
provide additional costimulatory signals besides secreting cytokines.
Almost all of these molecules proven to act in costimulation are also
considered to be involved in adhesion. The adhesion pathway mediated by
CD11/CD18 and its ligand ICAM-1 is one of the costimulatory pathways
best studied for T cells (33, 34, 35). Thus, anti-CD11/CD18 Abs were
found to inhibit anti-CD3-mediated T cell activation and
proliferation. In T cell-B cell heterotypic aggregation, analysis of
murine ICAM-1 expression mutants and ICAM-1-transfected B cells
indicated that alterations in the level of expression of ICAM-1
affected the efficiency with which a B cell can activate a T cell (19).
Also, induction of ICAM-1 on eosinophils enabled their binding to CD11
on T cells and, together with HLA-DR expression, induced Ag-specific T
cell proliferation (26). In agreement with the aforementioned previous
observations, we found in the present study that heterotypic
aggregation increased over time (Fig. 5) and was inhibited by the
introduction of anti-CD11/CD18 and anti-ICAM-1 Abs (Fig. 8);
however, when these Abs were introduced separately, the heterotypic
adhesion-induced histamine release was only partially inhibited (data
not shown). This suggests that besides ICAM-1 and CD11/CD18, other
adhesion molecules might be involved in the binding to T cells. VLA-4,
for instance, becomes important when CD11/CD18 is not activated
(36).
Mast cell-T cell heterotypic aggregation and histamine release required
activation of the 2B4 or the freshly isolated T cells (Figs. 1 and 2).
Indeed, it has been well demonstrated that CD11/CD18-dependent adhesion
of T cells to ICAM-1 requires activation of protein kinase C by
triggers such as phorbol esters or by cross-linking cell surface
molecules such as CD2 or CD3 with specific mAb or immobilized ligands
(33, 34, 35, 36, 37). Several surface molecules and receptors for
mediators/cytokines, such as PAF, IL-8, and MIP-1ß, are apparently
able to provide the first signal for CD11/CD18 activation (reviewed in
32 . The end result of this "inside-out" type of signaling is
integrin clustering, which leads to increased avidity, while the
CD11/CD18 membrane expression levels are thoroughly constant throughout
the activation process. However, the signals initiating adhesion
between CD11/CD18 and ICAM-1 are determined by the CD11/CD18 side of
the interaction causing alterations in the CD11/CD18 that enable it to
bind more avidly to ICAM-1 (32, 33, 34). It has been shown that
cross-linking of the TCR complex with anti-CD3 mAb results in a
protein kinase C-dependent cytoskeletal rearrangement involving an
association between CD11/CD18 and F-actin (38). Thus, as shown in other
cell systems, CD11/CD18-dependent adhesion of mast cells to T cells
depends on prior T cell activation.
TCR stimulation of CD11/CD18 avidity in cell-to-cell adhesion was found
to be transient (33, 34). In contrast, in this study, heterotypic
aggregation (and activation) increased over time (Figs. 4 and 5). It is
possible that adhesion-induced mast cell activation by T cells involves
induction of new proteins or other mediators that, in turn, generate a
new series of signals augmenting the avidity of CD11/CD18, thus leading
to an extended aggregation. Also, continuous adhesion might be possible
through interaction with other adhesion molecules that appear later in
the process, as was shown for leukocyte-endothelial cell interactions
mediated by selectins in early stages and by integrins later (39, 40).
The intracellular events and signal transduction pathways following
CD11/CD18-ICAM-1 interaction have more recently been investigated. It
has been shown that costimulation provided for anti-CD3-mediated
proliferation of T cells involves an extended CD11/CD18-ICAM-1
interaction leading to signal transduction events that result in
prolonged (>4-h) inositol phospholipid hydrolysis and a sustained
increase in free cytosolic calcium level (37). The CD11/CD18 signaling
was found to be mediated through a tyrosine kinase pathway that
stimulates tyrosine phosphorylation and activation of phospholipase
C-
1 (41). Of interest is the observation that costimulation of T
cells required a minimal period of 4 h of CD11/CD18-ICAM-1
interaction to provide maximal costimulation for anti-CD3-mediated
T cell activation (37). This observation might be relevant to the
relatively late onset of the effects of CD11/CD18-ICAM-1 interaction on
mast cell activation and mediator release observed in our study. Also,
when the other side of the interaction was analyzed, namely, when cell
activation pathways were examined in ICAM-1-bearing cells, it was found
that ICAM-1 adhesion is critical for lymphocyte adhesion-dependent
signal transduction in endothelial cells that involves inositol
phosphate generation and calcium mobilization (42). The mechanism(s)
involved in mast cell activation induced by heterotypic aggregation
noticed in this study has not yet been elucidated. A logical analogy is
T cell adhesion-dependent signaling, since these pathways have also
been described to be operative in mast cell signal transduction leading
to mediator release (43).
The demonstration that mast cells express multiple adhesion molecules
(reviewed in 44 has provided insight into possible adhesion
interactions between mast cells and extracellular matrix (ECM)
components or other cell types. Mature mast cells are found in tissues
where they execute specific biologic functions; interaction with ECM
may thus be assumed to be important for the migration into and for the
location of mast cells in tissues. Indeed, adhesion of mast cells to
laminin and fibronectin (45, 46) has been reported after mast cell
activation with PMA or Ag-mediated FcRI aggregation or in response
to c-kit ligand (47). Also, vascular cell adhesion
molecule-1 and VLA-4 are involved in mediating the adherence of mast
cells to cytokine-activated microvascular endothelium, an essential
step in cell migration from the intravascular compartment to the site
of inflammation (48). Furthermore, adhesion of mast cells to ECM
components transduces a variety of intracellular signals that regulate
cell function. These signals include protein tyrosine phosphorylation,
phosphoinositide hydrolysis, changes in intracellular calcium
concentration, and expression of several genes (reviewed in 49 .
Thus, the IL-3-induced DNA synthesis and proliferation of BMCMC is
augmented by integrin-mediated adherence to vitronectin (50). Cell
secretion is also modulated by adhesion to ECM. FcRI- or calcium
ionophore-mediated histamine release is augmented after the attachment
of RBL-2H3 cells to fibronectin (51). Coculture of mast cells with
fibroblasts also results in enhanced degranulation (reviewed in 49 . The mechanism(s) by which cell adhesion regulates secretion is not
fully understood; however, cell attachment results in cytoskeletal
changes, redistribution of secretory granules, and changes in protein
tyrosine phosphorylation, all of which might directly influence
degranulation (49). More recently, it has been shown that activated
murine lymphocytes induce promoter activity of the TCA3 gene
in mast cells following cell-to-cell contact (52).
The present study thus suggests that adhesion to activated T cells induces mast cell degranulation. Such lymphocyte-dependent mast cell activation would be expected to recruit mast cell mediators in the promotion of inflammation in the delayed phase of the allergic response. These would include increased vascular permeability, attracting additional cell types, and modulating lymphocyte function. Because mast cells are also known to reside in the periphery of lymph nodes and within thymus tissues, it is possible that lymphocyte-dependent mast cell activation at these sites could play a role in cell trafficking and regulation of cellular responses in these tissues. This effect might be exerted by adhesion alone or in concert with cytokines secreted from the activated T cells. The morphologic studies showing mast cells in close apposition to T cells, and the data presented in this study, thus indicate a heretofore-unrecognized pathway through which mast cells can be activated and degranulated in various T cell-mediated inflammatory responses.
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Acknowledgments |
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Footnotes |
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2 Abbreviations used in this paper: HSA, human serum albumin; BMCMC, murine bone marrow-derived mast cells; ECM, extracellular matrix; VLA, very late antigen.
Received for publication May 10, 1996. Accepted for publication December 12, 1997.
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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S. Nakae, H. Suto, M. Kakurai, J. D. Sedgwick, M. Tsai, and S. J. Galli Mast cells enhance T cell activation: Importance of mast cell-derived TNF PNAS, May 3, 2005; 102(18): 6467 - 6472. [Abstract] [Full Text] [PDF]
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 R. R. Sivalenka and R. Jessberger SWAP-70 Regulates c-kit-Induced Mast Cell Activation, Cell-Cell Adhesion, and Migration Mol. Cell. Biol., December 1, 2004; 24(23): 10277 - 10288. [Abstract] [Full Text] [PDF]
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J.-i. Kashiwakura, H. Yokoi, H. Saito, and Y. Okayama T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells J. Immunol., October 15, 2004; 173(8): 5247 - 5257. [Abstract] [Full Text] [PDF]
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 B. T. Edelson, Z. Li, L. K. Pappan, and M. M. Zutter Mast cell-mediated inflammatory responses require the {alpha}2{beta}1 integrin Blood, March 15, 2004; 103(6): 2214 - 2220. [Abstract] [Full Text] [PDF]
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R. Schramm, T. Schaefer, M. D. Menger, and H. Thorlacius Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone J. Leukoc. Biol., December 1, 2002; 72(6): 1122 - 1132. [Abstract] [Full Text] [PDF]
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D. Baram, G. G. Vaday, P. Salamon, I. Drucker, R. Hershkoviz, and Y. A. Mekori Human Mast Cells Release Metalloproteinase-9 on Contact with Activated T Cells: Juxtacrine Regulation by TNF-{alpha} J. Immunol., October 1, 2001; 167(7): 4008 - 4016. [Abstract] [Full Text] [PDF]
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D. Skokos, S. Le Panse, I. Villa, J.-C. Rousselle, R. Peronet, B. David, A. Namane, and S. Mecheri Mast Cell-Dependent B and T Lymphocyte Activation Is Mediated by the Secretion of Immunologically Active Exosomes J. Immunol., January 15, 2001; 166(2): 868 - 876. [Abstract] [Full Text] [PDF]
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 T. Biedermann, M. Kneilling, R. Mailhammer, K. Maier, C. A. Sander, G. Kollias, S. L. Kunkel, L. Hultner, and M. Rocken Mast Cells Control Neutrophil Recruitment during T Cell-mediated Delayed-type Hypersensitivity Reactions through Tumor Necrosis Factor and Macrophage Inflammatory Protein 2 J. Exp. Med., November 13, 2000; 192(10): 1441 - 1452. [Abstract] [Full Text] [PDF]
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V. H. Secor, W. E. Secor, C.-A. Gutekunst, and M. A. Brown Mast Cells Are Essential for Early Onset and Severe Disease in a Murine Model of Multiple Sclerosis J. Exp. Med., March 6, 2000; 191(5): 813 - 822. [Abstract] [Full Text] [PDF]
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 S. M. Singer and T. E. Nash T-Cell-Dependent Control of Acute Giardia lamblia Infections in Mice Infect. Immun., January 1, 2000; 68(1): 170 - 175. [Abstract] [Full Text] [PDF]
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