CXCR5+CD8+ T Cells: A Review of Their Antibody Regulatory Functions and Clinical Correlations
Steven M. Elzein, Jason M. Zimmerer, Jing Han, Bryce A. Ringwald, Ginny L. Bumgardner
Abstract
Abstract 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 Ab production. In this review, we provide an in-depth analysis of conflicting reports regarding the impact of CXCR5+CD8+ T cells on Ab production and examine the data supporting a role for Ab enhancement (B cell helper) and Ab downregulation (Ab-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 Ab responses. Coinhibitory molecule PD-1, among others, distinguishes CXCR5+CD8+ T cell subsets. We also provide, to our knowledge, 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.