Human CD4(+) T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses

The contribution of T helper (Th) and T cytotoxic (Tc) type 1 lymphocytes i n the expression of allergic contact dermatitis to haptens has been amply d ocumented. Conversely, the existence of T cell-based regulatory mechanisms has been poorly investigated. Here, we examined the properties of a subset of nickel-specific CD4(+) T cells displaying the cytokine profile (IL-10(++), IL-5(+++), IFN-gamma(+/-), IL4(+/-)) of T regulatory cells 1 (Tr1) and with;he potential to down-modulate immune responses to nickel. Tr1 clones w ere isolated from skin challenged with NiSO4 and peripheral blood of nickel -allergic patients, and from the blood of healthy individuals. Tr1 clones e xpressed CD25, CD28, CD30, CD26, and the IL-12 receptor beta 2 chain upon a ctivation, whereas the lymphocyte activation antigen-3 was present on 50% o f the clones. Monocytes precultured with Tr1 cells in the presence of nicke l, or treated with Tr1-derived supernatant, exhibited a markedly diminished capacity to stimulate nickel-specific Th1 responses. Tr1 supernatants also blocked the differentiation of dendritic cells (DC) from monocytes, as wel l as DC maturation and IL-12 production induced by lipopolysaccharide. As a consequence, the ability of DC to stimulate nickel-specific Th1 and Tc1 re sponses was greatly impaired. These inhibitory effects were completely prev ented by IL-10, but not IL-5, neutralization. In aggregate, the results ind icate that Tr1 cells can potently regulate the expression of Th1-mediated a llergic diseases via release of IL-10.