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

作者：el Bannoudi Hanane; Han Wanda G H; Stoop Jeroen N; Louis Plence Pascale; Huizinga Tom W J; Toes Rene E M^*

来源：European Journal of Immunology, 2013, 43(2): 439-446.

DOI：10.1002/eji.201242796

• DCs
• IL-10
• IL-12
• Immune regulation
• T cells

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- than CD4+ T cells primed by DCs exposed to either medium or DX5CD4+ T-cell supernatant. The addition of IL-12 to the co-culture with DX5+ DCs restores IFN- 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.

• 出版日期2013-2