Follicular CD8+ T cells: a novel subset in immune protection and antibody responses. (VAC3P.1062)

Abstract Endogenous antigen-specific CD8 T cells have been detected within B cell zones of the splenic white pulp during the primary response to multiple infections. The physiologic implications of CD8 T cell recruitment to B cell zones are unknown. However, such CD8 T cell localization may be beneficial for immunity in multiple ways, including, but not limited to: 1) direct CD8 T cell-mediated costimulation of B cells, 2) CD8 T cell-derived signals lowering the threshold of help required from CD4 follicular helper T cells (Tfh) for B cell maturation, and/or 3) direct CD8 T cell-mediated support of Tfh cells. We show here that after a combined TLR agonist and anti-CD40 antibody immunization (TLR/CD40) the follicular-homing CD8 T cell population is increased compared to infection, particularly at 2-3 days post-immunization. Concurrently, CD8 T cells upregulate Tfh cell-associated markers including CXCR5, PD-1, and ICOS. IL-21 is secreted robustly by CD8 T cells at this time point, which could help support B cell germinal center maintenance, class-switching, and Tfh cell differentiation. Indeed, in the context of TLR/CD40 immunization, the absence of CD8 T cells does not affect the IgM response, but reduces an isotype thought to be directed by IL-21, IgG2c, to levels seen in CD4 T cell-depleted animals. Our data indicates that CD8 T cells can assume a Tfh-like phenotype, we call follicular cytotoxic T cells (Tfc), early after challenge and direct antibody responses.