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

作者：Stankovic Sanda; Harpur Christopher M; Macleod Bethany L; Whitney Paul G; Gebhardt Thomas^*; Brooks Andrew G

来源：The Journal of Immunology, 2015, 195(10): 4892-4899.

DOI：10.4049/jimmunol.1500247

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.

• 出版日期2015-11-15