Human ab TCR sequencing of CD4+ and CD8+ memory and naive cells from healthy donors

Understanding how the size and content of TCR repertoire changes with age remains a critical challenge in immunobiology. Here, we report a longitudinal analysis of ab TCR repertoires of human T cells and subsets from 30 healthy adults aged from 28 to 85 at first visit and an average of 9-year follow-up as second visit by an UMI based RNAseq method. Through analysis of combined 2.0 x 108 naive and memory CD4+ and CD8+ T cells, we identified 1.1 x 106 and 2.8 x 106 unique TCRa and TCRb sequences. With advance of age, we observed 1) reduction of naive TCRa and TCRb repertoire richness more obvious than that of memory TCR repertoire richness particularly in naive CD8+ T cells; 2) significant increase of clonal expansion in CD8+ than in CD4+ T cells; 3) an increasing overlap of TCRa and TCRb sequences between two visits in CD8+ (more in memory than in naive cells) than in CD4+ T cells; and 4) increase overlap of TCR sequences between naive and memory cells at each visit more profound in CD8+ than in CD4+ T cells. These findings provide for the in vivo change of ab TCR repertoires in naive and memory CD4+ and CD8+ T cells with age and reveal that age associated increased stability of ab TCR repertoires in CD4+ and CD8+ T cells.