Figure 1. Distinct Mechanisms by which CXCR5⁺CD8⁺ T Cell Subsets Impact Humoral Immunity.

CXCR5⁺CD8⁺ T cell subsets are reported to mediate different effects upon antibody production. Antibody-enhancing CXCR5⁺CD8⁺ T cells express PD-1, ICOS, CD40L, and cytokines such as IFN-γ and IL-21. In vitro co-culture studies suggest that antibody-enhancing CXCR5⁺CD8⁺ T cells interact directly with antibody-producing B cells, or synergistically with CD4⁺ T_FH cells, to increase antibody production by antibody secreting cells (ASC). In contrast, one subset of CXCR5⁺CD8⁺ T cells that protects against autoimmunity is Qa-1 restricted (CD44⁺ICOSL⁺PD-1⁺CD122⁺Ly49⁺) and exerts cytotoxic killing of autoreactive CD4⁺ T_FH cells resulting in decreased autoantibody production. Another subset of antibody-suppressor CXCR5⁺CD8⁺ T cells (CD44⁺ICOSL⁻PD-1⁻IFN-γ⁺) is MHC-I restricted, antigen-specific, and directly mediates killing of allo-primed IgG⁺ B cells resulting in reduction of alloantibody production after transplant.