DX5+ CD4+ T cells modulate CD4+ T-cell response via inhibition of IL-12 production by DCs.

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]