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

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S. Laurent
P. Carrega
D. Saverino
P. Piccioli
M. Camoriamo
A. Morabito
B. Dozin
V. Fontana
R. Simone
L. Mortara
M.C. Mingari
G. Ferlazzo
M.P. Pistillo *
(*) Corresponding Author:
M.P. Pistillo | mariapia.pistillo@istge.it

Abstract

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.

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