Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1.

The ability of CD4 T cells to give rise to specialized T follicular helper cells (T FH ) critical to initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site of infection. In this study, we used a skin infection with HSV-1 characterized by the successive involvement of interconnected but distinct lymph nodes (LNs), to investigate the anatomical diversification of virus-specific CD4 T cell responses and the migratory capacity of T FH or their precursors. Whereas Th1 effector CD4 T cells expressing peripheral-targeting migration molecules readily migrated from primary to secondary reactive LNs, Bcl6 + CXCR5 + PD1 hi T FH were largely retained at the site of initial activation with little spillover into the downstream LNs involved at later stages of infection. Consistent with this, T FH maintained high-level surface expression of CD69, indicative of impaired migratory capacity. Notably, the biased generation and retention of T FH in primary LNs correlated with a preferential generation of germinal centers at this site. Our results highlight a limited anatomical diversification of T FH responses and germinal center reactions that were imprinted within the first few cell divisions during T FH differentiation in LNs draining the site of initial infection.