Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells

Luksch, Claudia R.; Winqvist, Ola; Ozaki, Minette E.; Karlsson, Lars; Jackson, Michael R.; Peterson, Per A.; Webb, Susan R.

doi:10.1073/pnas.96.6.3023

Cited by 73 publications

(63 citation statements)

References 32 publications

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“…ICAM-1 expressed on accessory cells was also shown to suppress Th2 cytokine production of naive CD4 ϩ T cells (47). Because costimulation of T cells with ICAM-1 was shown to augment CTLA-4 expression (48), the effect of ICAM-1/-2 on the suppression of Th2 differentiation or of Th2 cytokine production mentioned above could be mediated by the augmentation of CTLA-4 expression on CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

Polarization of Naive CD4+ T Cells Toward the Th1 Subset by CTLA-4 Costimulation

Kato

Nariuchi

2000

The Journal of Immunology

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In this study, we examined in vitro the role of CTLA-4 costimulation in the polarization of naive CD4+ T cells toward the Th1 subset. When CTLA-4 costimulation was blocked by the inclusion of anti-CTLA-4 Fab in cultures during priming of naive CD4+ T cells with anti-CD3 in the presence of splenic adherent cells, they were polarized toward the Th2 subset. Conversely, the engagement of CTLA-4 with immobilized anti-CTLA-4 or with CD80-P815 cells polarized naive CD4+ T cells costimulated with anti-CD3 and anti-CD28 toward the Th1 subset. The CTLA-4 costimulation during priming augmented TGF-β1 mRNA accumulation in naive CD4+ T cells, and the inclusion of anti-TGF-β in cultures for priming suppressed the effect of CTLA-4 costimulation on the Th1 polarization. The addition of low doses of TGF-β1 in cultures for priming of naive CD4+ T cells enhanced the production of Th1 cytokines upon secondary stimulation, although Th2 cytokine production was not affected by the doses of TGF-β1. The CTLA-4 costimulation was also shown to suppress IL-4 production of naive CD4+ T cells upon priming. These results indicate that the costimulation against CTLA-4 drives polarization of naive CD4+ T cells toward the Th1 subset independent of IL-12 through, at least in part, the enhancement of TGF-β1 production, and it also hampers Th2 subset differentiation by affecting IL-4 production of naive CD4+ T cells.

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Section: Discussionmentioning

confidence: 99%

Polarization of Naive CD4+ T Cells Toward the Th1 Subset by CTLA-4 Costimulation

Kato

Nariuchi

2000

The Journal of Immunology

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“…There is both direct and indirect evidence that LFA-1 signals may influence T cell cytokine profiles. LFA-1 signaling has been implicated as directly promoting Th1-like responses and/or inhibiting Th2 immunity (22,49). Thus, a potential consequence of anti-LFA-1 therapy may be the direct inhibition of IFN-␥ and corresponding induction of IL-4 production by donor-reactive T cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-LFA-1 Therapy Induces Long-Term Islet Allograft Acceptance in the Absence of IFN-γ or IL-4

Nicolls

Coulombe

Yang

et al. 2000

The Journal of Immunology

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mAb therapy directed against a variety of cell surface accessory molecules has been effectively utilized to prolong allograft acceptance in various models of tissue and organ transplantation. The purpose of this study was to determine whether transient therapy directed against the adhesion molecule LFA-1 (CD11a) was sufficient to induce donor-specific tolerance to pancreatic islet allografts. Anti-LFA-1 monotherapy was found to be efficacious in inducing long-term islet allograft acceptance in multiple donor-recipient strain combinations. Graft acceptance following anti-LFA-1 therapy was not simply due to clonal ignorance of donor Ags in that the majority of recipients bearing established islet allografts resisted rejection induced by immunization with donor-type APCs. Furthermore, donor-specific tolerance from anti-LFA-1-treated animals could be transferred to secondary immune-deficient animals. Taken together, these results indicated that transient anti-LFA-1 monotherapy resulted in donor-specific tolerance. In vitro, functionally tolerant animals retained normal anti-donor reactivity as assessed by proliferative, cytotoxic, and cytokine release assays that demonstrated that tolerance was not secondary to general clonal deletion or anergy of donor-reactive T cells. Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-γ-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-γ and IL-4, respectively, in contrast to results in other transplantation models.

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“…Dros cell lines expressing murine MHC H2-A d molecules ϩ͞Ϫ murine ICAM-1 and͞or B7.2 molecules were generated as described (19,20). Briefly, cDNA clones for B7.2, ICAM-1, and H2-A d ␣ and ␤ chains were expressed in Dros Schneider SC2 cells under the control of a metallothionein promoter.…”

Section: Methodsmentioning

confidence: 99%

“…Culture supernatant was removed from the above cultures before pulsing with [ 3 H]thymidine for analysis of cytokine accumulation. Cytokines were measured by using a sandwich ELISA assay as described (20). Both capture antibodies and biotinylated detection antibodies were obtained from PharMingen; recombinant cytokines used for construction of standard curves were either from Genzyme or PharMingen.…”

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confidence: 99%

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Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells

Ragazzo¹

2000

Proceedings of the National Academy of Sciences

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The mechanisms controlling induction of anergy at the level of naïve CD4 ؉ T cells are poorly understood but thought to reflect limited contact with costimulatory molecules during T cell antigen receptor (TCR) ligation. To clarify this question, naïve TCR transgenic CD4 ؉ cells were exposed to specific peptide presented by transfected antigen-presenting cells (APC) expressing MHC class II molecules with defined accessory molecules. Significantly, culturing CD4 ؉ cells with APC expressing MHC II plus peptide alone elicited early TCR signaling but failed to induce either proliferation or anergy. Culture with APC expressing MHC II plus B7 molecules led to strong proliferation and T cell priming but no anergy. In marked contrast, conspicuous induction of anergy occurred after T cell culture with APC expressing MHC class II and intercellular adhesion molecule-1 (ICAM-1). Thus, at the level of naïve CD4 ؉ cells, anergy induction appears to reflect selective contact with APC expressing ICAM-1 in the absence of B7.rodent ͉ adhesion molecules T he outcome of initial T cell contact with antigen (immunity or tolerance) is important both for assuring adequate responses to infectious pathogens and preventing inappropriate responses to self-antigens. The mechanisms controlling self͞nonself discrimination are not fully understood but may hinge on the function of costimulatory molecules. For normal immune responses, it is clear that T cell stimulation involves not only T cell receptor (TCR) recognition of peptide-MHC complexes but also interactions between costimulatory receptors and their ligands on professional antigen-presenting cells (APC). CD28 molecules are the bestcharacterized costimulatory receptors on T cells. Binding of CD28 to its B7 ligands complements TCR ligation to promote immunological synapses between T cells and APC (1, 2) and ultimately the induction of sustained proliferative responses, cytokine production (e.g., IL-2 and IL-4), and expression of molecules promoting cell survival (e.g., Bcl-x L ) (3-8).When T cells recognize antigen in the absence of costimulation, however, the results are quite different. For primed T cells, TCR stimulation (signal 1) without concomitant coligation of CD28 (signal 2) induces T cell functional unresponsiveness or anergy characterized by the failure to proliferate or make IL-2 on reexposure to antigen presented in the context of optimal costimulation (8-12).Although this paradigm for anergy induction is well established for T cell clones and lines, there is considerable controversy as to whether delivery of signal 1 alone also induces anergy at the level of naïve CD4 ϩ T cells. In the studies of Lechler and colleagues (13), exposure of unprimed CD4 ϩ T cells to immobilized anti-CD3 mAb was shown to render the surviving cells profoundly unresponsive to subsequent mitogen stimulation. The relevance of this finding to physiological recognition of MHC-peptide on normal APC is somewhat unclear, because the affinity of the TCR for peptide-MHC complexes is more than 1,000-fold lowe...

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Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells

Cited by 73 publications

References 32 publications

Polarization of Naive CD4+ T Cells Toward the Th1 Subset by CTLA-4 Costimulation

Polarization of Naive CD4+ T Cells Toward the Th1 Subset by CTLA-4 Costimulation

Anti-LFA-1 Therapy Induces Long-Term Islet Allograft Acceptance in the Absence of IFN-γ or IL-4

Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells

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