Loss of CD127 expression links immune activation and CD4+ T cell loss in HIV infection

Although chronic immune activation correlates with CD4+ T cell loss in HIV infection, an understanding of the factors mediating T cell depletion remains incomplete. We propose that reduced expression of CD127 (IL-7 receptor α chain, IL-7Rα), induced by immune activation, contributes to CD4+ T cell loss in HIV infection. In particular, loss of CD127 on central memory CD4+ T cells (TCM) severely restrains the regenerative capacity of the memory component of the immune system, resulting in a limited ability to control T cell homeostasis. Studies from both pathogenic and controlled HIV infection indicate that the containment of immune activation and preservation of CD127 expression are critical to the stability of CD4+ T cells in infection. A better understanding of the factors regulating CD127 expression in HIV disease, particularly on TCM cells, might unveil new approaches exploiting the IL-7/IL-7R receptor pathway to restore T cell homeostasis and promote immune reconstitution in HIV infection.