Defective CD4 T cell cognate helper functions in response to influenza immunization and infection in aged mice (47.8)

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Abstract A poor immune response is a hallmark of aging. Older individuals are more susceptible to infections and respond poorly to new immunization. This is caused, at least in part, by a defective antibody response. We have shown that age-associated defects impair CD4 T cell functions. Since an optimal antibody response requires good CD4 cognate help through T follicular helper (Tfh) cells, we aimed to determine whether the impaired cognate help resulted from defects in the generation and/or functions of Tfh cells in aged mice. The work presented herein shows that the generation of Tfh cells in response to influenza immunization is delayed, reduced and shortened in aged mice compared to young mice. Also fewer Tfh cells are generated in aged mice than in young mice following influenza infection. The Tfh cells generated in aged mice, however, express similar levels of IL-21, BCL-6, CXCR5 and IL-4 mRNA than Tfh cells from young mice. These data suggest that the generation rather than the functions of Tfh cells is impaired in aged mice. The addition of poly(I:C) as an adjuvant to the influenza vaccine increases Tfh generation and antibody production in young and aged mice. We are investigating the mechanisms by which TLR ligands improve the Tfh response.