γδ T Cells Enhance the Expression of Experimental Autoimmune Encephalomyelitis by Promoting Antigen Presentation and IL-12 Production

Abstract

Using an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP)-reactive lymph node cells (LNC), we have shown that depletion of γδ T cells from LNC resulted in diminished severity of EAE in recipient mice, both clinically and histopathologically. The reduced potency of γδ T cell-depleted LNC to induce EAE correlated with decreased cell proliferation in response to MBP. The γδ T cell effect upon the threshold of MBP-induced LNC proliferation and EAE transfer was restored by reconstitution of γδ T cells derived from either MBP-immunized or naive mice, indicating that this effect was not Ag specific. The enhancing effect of γδ T cells on MBP-induced proliferation and EAE transfer required direct cell-to-cell contact with LNC. The γδ T cell effect upon the LNC response to MBP did not involve a change in expression of the costimulatory molecules CD28, CD40L, and CTLA-4 on TCRαβ+ cells, and CD40, CD80, and CD86 on CD19+ and CD11b+ cells. However, depletion of γδ T cells resulted in significant reduction in IL-12 production by LNC. That γδ T cells enhanced the MBP response and severity of adoptive EAE by stimulating IL-12 production was supported by experiments showing that reconstitution of the γδ T cell population restored IL-12 production, and that γδ T cell depletion-induced effects were reversed by the addition of IL-12. These results suggest a role for γδ T cells in the early effector phase of the immune response in EAE.