To further characterize this T-cell population,

To further characterize this T-cell population, PF-01367338 purchase 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. The immune system can protect the host against the detrimental effects of a broad range of pathogenic microorganisms

and, at the same time, maintain the tolerance to self-antigens. Triggering an immune response to self-antigens can result in the induction of autoimmunity. The induction of autoimmunity and the damage it can cause is, among others, controlled by the presence and action of suppressor T cells [1-5]. Several populations of CD4+ T cells have been described that are involved in the maintenance of self-tolerance and prevention of autoimmunity and inflammation. The most prominent Nutlin-3 concentration and well-studied T-cell population

with regulatory properties is characterized by the expression of the transcription factor Foxp3. These cells have been shown to posses the ability to influence different types of immune responses such as inhibiting the proliferation and/or cytokine production of effector T cells [6-11]. Likewise, they have also been reported to influence the differentiation of naive CD4+ T cells into IL-10 or TGF-β-producing adaptive Treg cells [12]. Furthermore, these cells can alter the function of APCs through inhibition of their antigen presenting activity, proinflammatory chemokine production, and expression of co-stimulatory molecules [13-20]. Other T-cell subsets also have the ability to influence the outcome of immune responses that affect the integrity of the body. For example, a population of T cells characterized by the expression of CD49b [21] that we will call DX5+CD4+ T cells, has been shown to alleviate diabetes, as well as collagen-induced arthritis (CIA) and delayed-type hypersensitivity reactions in mice [21-23]. CD49b is an β-2 integrin and is not only expressed by a subpopulation of CD4+ and CD8+ T cells, but also on NKT cells.

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