Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses

T follicular helper (T(FH)) cell responses are essential for generation of protective humoral immunity during influenza infection. Aging has a profound impact on CD4(+) T cell function and humoral immunity, yet the impact of aging on antigen specific T(FH) responses remains unclear. Influenza specific T(FH) cells are generated in similar numbers in young and aged animals during infection, but T(FH) cells from aged mice exhibit significant differences, including reduced expression of ICOS and elevated production of IL-10 and IFNγ, which potentially impairs interaction with cognate B cells. Also, more influenza specific T cells in aged mice have a regulatory phenotype, which could contribute to the impaired T(FH) function. Adoptive transfer studies with young T cells demonstrated that TGF-β1 in the aged environment can drive increased regulatory T cell accumulation. Aging and the aged environment thus impact antigen specific T(FH) cell function and formation, which contribute to reduced protective humoral responses.