Increased B7-H1 expression on dendritic cells correlates with PD-1 expression on T cells in SIV-infected macaques and may contribute to T cell dysfunction and disease progression

摘要

Suppression of dendritic cell function in HIV-1 infection is thought to contribute to inhibition of immune responses and disease progression, but the mechanism of this suppression remains undetermined. Using the rhesus macaque model, we show B7-H1 (PD-L1) is expressed on lymphoid and mucosal dendritic cells (both myeloid DC and plasmacytoid DC) and its expression significantly increases after SIV infection. Meanwhile, its receptor, PD-1 is upregulated on T cells in both peripheral and mucosal tissues, and maintained at high levels on SIV-specific CD8+ T cell clones in chronic infection. However, both B7-H1 and PD-1 expression in SIV controllers was similar to controls. Expression of B7-H1 on both peripheral mDCs and pDCs positively correlated with levels of PD-1 on circulating CD4+ and CD8+ T cells, viremia and declining peripheral CD4+ T cells levels in SIV-infected macaques. Importantly, blocking DCs B7-H1 interaction with PD-1+ T cells could restore SIV-specific CD4+ and CD8+ T cell function as evidenced by increased cytokine secretion and proliferative capacity. Combined, the results indicate interaction of B7-H1/PD-1 between APCs and T-cell correlates with impairment of CD4+T-helper cells and CTL responses in vivo, and all are associated with disease progression in SIV infection. Blockade of this pathway may have therapeutic implications for HIV-infected patients.