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DX5+ CD4+ T cells have been shown to dampen collagen-induced arthritis and delayed-type hypersensitivity reactions in mice. These cells are also potent modulators of T-helper cell responses through direct effects on CD4+ T cells in an IL-4 dependent manner. To further characterize this T-cell population, we studied their effect on DCs and the potential consequences on T-cell activation. Here, we show that mouse DX5+ CD4+ T cells modulate DCs by robustly inhibiting IL-12 production. This modulation is IL-10 dependent and does not require cell contact. Furthermore, DX5+ CD4+ T cells modulate the surface phenotype of LPS-matured DCs. DCs modulated by DX5+ CD4+ T-cell supernatant express high levels of the co-inhibitor molecules PDL-1 and PDL-2. OVA-specific CD4+ T cells primed with DCs exposed to DX5+ CD4+ T-cell supernatant produce less IFN-γ than CD4+ T cells primed by DCs exposed to either medium or DX5− CD4+ T-cell supernatant. The addition of IL-12 to the co-culture with DX5+ DCs restores IFN-γ production. When IL-10 present in the DX5+ CD4+ T-cell supernatant is blocked, DCs re-establish their ability to produce IL-12 and to efficiently prime CD4+ T cells. These data show that DX5+ CD4+ T cells can indirectly affect the outcome of the T-cell response by inducing DCs that have poor Th1 stimulatory function. [ABSTRACT FROM AUTHOR]

CD4 [ABSTRACT FROM AUTHOR]

CD4 T cells are important for CD8 T-cell priming by providing cognate signals for DC maturation. We analyzed the capacity of CD4 T cells to influence CD8 T-cell responses induced by activated DC. Surprisingly, mice depleted for CD4 cells were able to generate stronger antigen-specific CD8 T-cell responses after DC vaccination than non-depleted mice. The same observation was made when mice were vaccinated with MHC class II DC, indicating the presence of a MHC class II-dependent CD4 T-cell population inhibiting CD8 T-cell responses. Recently we described the expansion of DX5CD4 T cells, a T-cell population displaying immune regulatory properties, upon vaccination with DC. Intriguingly, we now observe an inverse correlation between CD8 T-cell induction and expansion of DX5CD4 T cells as the latter cells did not expand after vaccination with MHC class II DC. In vitro, DX5CD4 T cells were able to limit proliferation, modulate cytokine production and induce Foxp3 expression in OVA-specific CD8 T cells. Together, our data show an inhibitory role of CD4 T cells on the induction of CD8 T-cell responses by activated DC and indicate the involvement of DX5CD4, but not CD4CD25, T cells in this process. [ABSTRACT FROM AUTHOR]