CD8 follicular T cells provide helper and cytolytic function in the B cell follicule during antibody-mediated autoimmunity

Abstract

Abstract CXCR5+ CD8 T cells arise during situations of chronic antigen and inflammation, including chronic viral infection, cancer, and antibody-mediated autoimmunity. In some conditions CXCR5 expression facilitates CD8 T cell homing to B cell follicles, while some studies find persistent CCR7 expression prevents follicle entry. Despite robust research within this fairly new field variance in tissue localization, expression profiles, inflammatory conditions and developmental stages limit comparisons between existing CXCR5+CD8 T cell studies. We demonstrate that CXCR5+PD-1+ CD8 T follicular (Tfc) cells comprise a functionally non-redundant subset of CXCR5+ CD8 T cells in systemic autoimmune disease. CD8 Tfc develop in the absence of functional Tregs and expand during lymphoproliferation. CD8 Tfc acquire the capacity to produce helper cytokines including co-expression of IL-21 and IL-4, and maintain capacity for cytolytic function expresing granzyme B and TNFα, suggesting the potential for functional mechanisms that diverge from CD4 Tfh cells. IL-4+IL-21+ CD8 Tfc localization in the follicle and germinal center suggest that CD8 Tfc may promote B cell activities in either location during autoimmune disease. B cell activities influenced by CD8 Tfc cells are not fully defined such as regulating somatic mutation, memory and plasma cell differentiation, and germinal center movement. However CD8 T cells promote plasma cell differentiation and antibody class switch, but do not alter germinal center B cell numbers. CD8 Tfc position coupled with cytokine production in the germinal center and follicle, and induction of activation-induced cytidine deaminase by B cells suggest a dominant helper-like role with cytolytic potential.