The Differentiation and Maintenance of SARS-CoV-2-Specific Follicular Helper T Cells

Upon acute viral infection, virus-specific CD4(+) T cells differentiate into either T(H)1 cells or follicular helper T (T-FH) cells. The molecular pathways governing such bimodal cell fate commitment remain elusive. Additionally, effector virus-specific T-FH cells further differentiate into corresponding memory population, which confer long-term protection against re-infection of same viruses by providing immediate help to virus-specific memory B cells. Currently, the molecular mechanisms underlying the long-term maintenance of memory T-FH cells are largely unknown. In this review, we discuss current understanding of early differentiation of virus-specific effector T-FH cells and long-term maintenance of virus-specific memory T-FH cells in mouse models of viral infection and patients of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.