Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

摘要: A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing diversity has been implicated in the age-associated decline CD8 immunity. In this study, using well-characterized mouse influenza virus model, we show that although comparable numbers of cells are elicited lung airways young aged mice after de novo infection, majority exhibit profound shifts epitope immunodominance restricted TCR responding cells. preferential reactivity viral epitopes with low naive precursor frequency was observed, some cases leading “holes” repertoire. These effects were also seen thymectomized mice, consistent role thymus maintaining diversity. Furthermore, generally correlated impaired responses heterosubtypic challenge. This study formally demonstrates infection model naturally occurring contraction can result known immunodominant observations have important implications design vaccine strategies elderly.