CTLA-4 expressed by human dendritic cells modulates thei cytokine secretion and induction of T cell proliferation

CTLA-4 is the major nefative regulator of T cell response. We have analyzed the expression of CTLA-4 in human monocytes and monocyte-derived DCs and the effects of its engagement on cytokine production and T cell stimulatory activity by mature DCs (mDCs). We found the CTLA-4 was highly expressed on freshly isolated monocytes, then down-modulated on the immature DCs (iDCs) and upregulated on mDCs. Treatment of mDCS with an agonistic anti-CTLA-4 m Ab enhanced secretion of IL-10 but reduced secretion of IL-8 and IL-12, as well as autologous CD4* T-cell proliferation in response to simulation with PPD recall antigenloaded-DCs. Neutralization of IL-10 with an anti-IL-10 antibody partially restored the ability of anti-CTLA-4-treated mDCs to stimulate T cell proliferation in response to PPD. Our data provide the first evidence that CTLA-4 receptor is expressed by human mDCs and exerts immune modulatory effects in these cells.