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 maintained by division of mature lymphocytes. Recent studies suggest that peripheral T cell expansion may be driven by low-affinity interactions with self ligands. Here we have investigated the consequence of homeostatic proliferation on the T cell repertoire. Following day 3 thymectomy of mice, there is a subsequent 30-fold expansion of the peripheral T cell population. Significantly, expansion of the T cell population results in skewed TCR Vbeta complementarity-determining region (CDR)3 length distributions and, in some cases, a marked bias toward one or two CDR3 lengths. TCR sequence analysis showed that these biases were a consequence of (oligo)clonal T cell expansion. Neonatally thymectomized adult mice have reduced antibody responses to primary challenge with T-dependent antigens. These data demonstrate that peripheral expansion of the T cell pool can result in a limited T cell repertoire, indicating that the array of stimulating ligands that drives homeostatic expansion is restricted.