CXCR5+CD8+ T Cells: A Review of Their Antibody Regulatory Functions and Clinical Correlations

CD8 + T cells have conventionally been studied in relationship to pathogen or tumor clearance. Recent reports have identified novel functions of CXCR5 + CD8 + T cells that can home to lymphoid follicles, a key site of antibody production. In this review we provide an in-depth analysis of conflicting reports regarding the impact of CXCR5 + CD8 + T cells on antibody production and examine the data supporting a role for antibody-enhancement (B cell "helper") and antibody-downregulation (antibody-suppressor) by CXCR5 + CD8 + T cell subsets. CXCR5 + CD8 + T cell molecular phenotypes are associated with CD8-mediated effector functions including distinct subsets that regulate antibody responses. Co-inhibitory molecule PD-1, among others, distinguish CXCR5 + CD8 + T cell subsets. We also provide the first in-depth review of human CXCR5 + CD8 + T cells in the context of clinical outcomes and discuss the potential utility of monitoring the quantity of peripheral blood or tissue infiltrating CXCR5 + CD8 + T cells as a prognostic tool in multiple disease states.