Sudhir Gupta
University of California, USA
Title: CD8+ Treg in health and primary immunodeficiency diseases
Biography
Biography: Sudhir Gupta
Abstract
In past few years, seminal experiments in mice models of human diseases provided strong evidence of the presence of natural CD8+ T regulatory cells (CD8 Treg). The role of CD8+ Treg was subsequently shown in the control of several autoimmune disease models. Shi and associates have reported that human CD8+CXCR3+ (CD183+) T cells have same function as murine CD8+CD122+ Treg. We have investigated a role of CD8+ T cells in regulating various functions of autologous and allogeneic CD4+ T cells. CD8 T reg inhibit cell division and DNA synthesis of autologous CD4+ T cells, and differentiation of naïve CD4+ to effector memory CD4+ (TEM) and CD45RA+ terminally differentiated effector memory/exhausted CD4+ T cells (TEMRA). CD8+ Treg mediates their regulatory effect, at least in part, by IL-10 and MIP1β, and not due to direct cytotoxicity/apoptosis of CD4+ T cells. CD8+ T cells inhibit secretion IL-17A, IL-10, and IFN-γ by autologous CD4+ T cells. Furthermore, CD8 Treg inhibits induction of FoxP3 in CD4+ T cells. Therefore, CD8+ Treg are regulators of regulatory CD4+ T cells. CD8+Treg were further characterized phenotypically, and appear to be CD8+CCR7+CD25hiICOS+CTLA-4+FoxP3+ phenotype. CD8+ Treg in primary immunodeficiency diseases and human aging will be discussed.