CD4+ T Cells Regulate CD8+ T Cell-Mediated Cutaneous Immune Responses by Restricting Effector T Cell Development through a Fas Ligand-Dependent Mechanism

Abstract

The magnitude and duration of CD8+ T cell-mediated responses in the skin to hapten sensitization and challenge, contact hypersensitivity (CHS), is negatively regulated by CD4+ T cells through an unknown mechanism. In this study we show that CD4+ T cells restrict the development and expansion of hapten-specific CD8+ T cells mediating CHS responses to 2,4-dinitrofluorobenzene. In the absence of CD4+ T cells, high numbers of hapten-specific CD8+ T cells producing IFN-γ were detected in the skin-draining lymph nodes on day 5 postsensitization, and these numbers decreased slightly, but were maintained through day 9, correlating with the increased magnitude and duration of CHS responses observed in these mice. In the presence of CD4+ T cells, the number of hapten-specific CD8+ T cells producing IFN-γ detected on day 5 postsensitization was lower and quickly fell to background levels by day 7. The limited development of effector CD8+ T cells was associated with decreased numbers of hapten-presenting dendritic cells in the lymphoid priming site. This form of immunoregulation was absent after sensitization of Fas ligand-defective gld mice. Transfer of wild-type CD4+ T cells to gld mice restored the negative regulation of CD8+ T cell priming and the immune response to hapten challenge in gld-recipient mice. These results indicate that CD4+ T cells restrict hapten-specific CD8+ T cell priming for CHS responses through a Fas ligand-dependent mechanism.

Interactions between CD47 and Thrombospondin Reduce Inflammation

“…Recently it has been shown that CD47 enhances Fas-mediated cytotoxicity (14). Our data fit well with these results because it is likely that the absence of CD47 might, on the one hand, suppress BNIP-3 up-regulation and thus susceptibility to activation-induced cell death and, on the other, decrease Fas-dependent mechanisms involved in cutaneous hypersensitivity (58,59). Notably, these two mechanisms are not mutually exclusive but might take place simultaneously in the model we describe here.…”

CD43 Collaborates with P-Selectin Glycoprotein Ligand-1 to Mediate E-Selectin-Dependent T Cell Migration into Inflamed Skin

“…Additional work will be required to clarify the role of CD43 in CD8 ϩ T cell migration. Among CD4 ϩ T cells, a population that negatively regulates CHS responses has been reported (33,34). The observation that ear swelling is normal in DKO mice, despite the reduced CD4 ϩ T cell infiltration into the inflamed ear, may suggest that PSGL-1 and CD43 are also involved in the infiltration of these regulatory CD4 ϩ T cells.…”

Eczéma allergique de contact : Comment ré-induire une tolérance ?

“…En dehors de l'IL-10, d'autres mécanismes de l'effet régulateur des LT CD4 + existent, notamment celui impliquant la sécrétion ou l'excrétion de TGFβ à la membrane des LT à fonctions régulatrices [21]. Par ailleurs, les cellules T CD4 + pourraient réguler la réponse inflammatoire en éliminant les cellules présentant l'haptène dans les ganglions lymphatiques au cours de la phase de sensibilisation, via un mécanisme dépendant de Fas-ligand, limitant ainsi l'activation des LT CD8 + pré-curseurs [22].…”