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

First Author  el Bannoudi H Year  2013
Journal  Eur J Immunol Volume  43
Issue  2 Pages  439-46
PubMed ID  23169063 Mgi Jnum  J:192816
Mgi Id  MGI:5466616 Doi  10.1002/eji.201242796
Citation  El Bannoudi H, et al. (2013) DX5(+) CD4(+) T cells modulate CD4(+) T-cell response via inhibition of IL-12 production by DCs. Eur J Immunol 43(2):439-46
abstractText  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-gamma 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-gamma 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.
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