Peripheral T cell lymphopenia and concomitant enrichment in naturally arising regulatory T cells:: The case of the pre-Tα gene-deleted mouse

In pre-T alpha (pT alpha) 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 pT alpha(-/-) peripheral T cell phenotype could be reproduced with normal cells. In the pT alpha(-/-) thymus and peripheral lymphoid organs, FoxP3(+)CD4(+) cells were enriched. Parabiosis experiments showed that many pT alpha(-/-)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 pT alpha(-/-) 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.