PD-1 and ICOS are coexpressed in T follicular helper cells but define three stages of maturation of T follicular regulatory cells
- Filipa Ribeiro
- Diogo Antunes
- Ana R. Pires
- José Rino
- Beatriz Filipe
- Kátia Jesus
- Ricardo Correia
- Válter R. Fonseca
- Saumya Kumar
- Luis Graca
2025-07-11
Humoral responses to infection or vaccination require T cell–B cell interactions. T follicular helper (T FH ) cells drive germinal center (GC) responses by providing help to B cells, whereas T follicular regulatory (T FR ) cells regulate them. Both mature GC–located T FH and T FR cells are widely characterized by the expression of ICOS and PD-1. However, although human T FR cells share many phenotypic characteristics with T FH cells, we found that ICOS and PD-1 are up-regulated differently in each. Although T FH cells express these proteins synchronously during maturation, they define three maturation stages in T FR cells. T FR cells in an intermediate maturation stage express ICOS, and it is only at the last stage of differentiation that both molecules are expressed at high levels. Although most T FR cells within the B cell follicle are PD-1 − , the T FR within the GC are ICOS + PD-1 + . These results show that T FH and T FR cells within human lymphoid tissue follow distinct maturation stages.