Human Placental Pericytes Poorly Stimulate and Actively Regulate Allogeneic CD4 T Cell Responses

Abstract

Objective— Cell-mediated immune responses in peripheral tissues begin with T cell infiltration through endothelial cell (EC) microvessels and accumulation in the perivascular space occupied by pericytes (PC). Here, we investigate how human T cells interact with PC. Methods and Results— We compared human placental PC with autologous umbilical vein EC. Cultured PC express lower levels of major histocompatibility complex (MHC) and positive costimulatory molecules but higher levels of negative costimulatory molecules than do EC. Unlike EC, interferon-γ-treated MHC class II–positive PC (PC + ) cannot stimulate resting allogeneic CD4 T cell proliferation or cytokine production. Instead, coculture of resting CD4 T cells with PC + induces CD25 expression and renders T cells unresponsive to restimulation by EC + from the same donor. PC cultured across a semi-permeable membrane decrease alloreactive CD4 T cell proliferation to EC + , an effect enhanced by pretreatment of PC with interferon-γ and partially reversed by interleukin-10 and transforming growth factor-β neutralization, but do not induce anergy. Conclusion— Human placental PC are poorly immunogenic and negatively regulate CD4 T cell responses through contact-dependent and contact-independent mechanisms.