Peripheral T cell expansion in lymphopenic mice results in a restricted T cell repertoire

In the absence of thymic contribution, the peripheral T cell pool is mainta ined by division of mature lymphocytes. Recent studies suggest that periphe ral T cell expansion may be driven by few-affinity interactions with self l igands. Here we have investigated the consequence of homeostatic proliferat ion on the T cell repertoire. Following day 3 thymectomy of mice, there is a subsequent 30-fold expansion of the peripheral T cell population. Signifi cantly, expansion of the T cell population results in skewed TCR V beta com plementarity-determining region (CDR)3 length distributions and, in some ca ses, a marked bias toward one or two CDR3 lengths. TCR sequence analysis sh owed that these biases were a consequence of(oligo)clonal T cell expansion. Neonatally thymectomized adult mice have reduced antibody responses to pri mary challenge with T-dependent antigens. These data demonstrate that perip heral expansion of the T cell pool can result in a limited T cell repertoir e, indicating that the array of stimulating ligands that drives homeostatic expansion is restricted.