Peripheral T Cell Lymphopenia and Concomitant Enrichment in Naturally Arising Regulatory T Cells: The Case of the Pre-Tα Gene-Deleted Mouse

Abstract

In pre-Tα (pTα) gene-deleted mice, the positively selectable CD4+CD8+ double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25+FoxP3+ regulatory T cells. Using mixed bone marrow chimeras, where thymic output was 1% normal, the pTα−/− peripheral T cell phenotype could be reproduced with normal cells. In the pTα−/− thymus and peripheral lymphoid organs, FoxP3+CD4+ cells were enriched. Parabiosis experiments showed that many pTα−/−CD4+ single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pTα−/− mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.