CD8 T follicular cell function in autoimmune disease

Abstract

Abstract Autoimmune disease comprises more than 80 well characterized disorders that affect 24 million Americans and many of these disorders are characterized by the presence of high-affinity auto-antibodies. The production of these high-affinity antibodies requires activation, affinity maturation, and differentiation of B cells into class-switched plasma cells. This process occurs within the germinal center and requires the help of specialized T follicular helper (Tfh) cells. Traditionally, Tfh are CD4 T cells that become activated and differentiate, acquiring the surface proteins required to migrate into the germinal center and interact directly with B cells to induce germinal center responses. Recently, a population of CD8 T follicular (Tfc) cells that are phenotypically similar to CD4 Tfh have been described in chronic viral infection, cancer, and autoimmune disease. These cells have been shown to function similarly to CD4 Tfh cells as well as cytotoxic CD8 T cells under various conditions. Further, the mechanism and localization of CD8 Tfc cell function in autoimmune disease has not yet been investigated. Using immunofluorescence CD8 Tfc cells were found to localize and produce cytokines in the B cell follicle and germinal center in autoimmune disease. Indirect co-culture of CD8 Tfc cells with B cells show that while CD8 produced IL-21 does not influence B cell function, CD8 produced IL-4 does. This data indicates that CD8 Tfc and CD4 Tfh cells may rely on slightly different mechanisms to influence B cell function within and without the germinal center.