Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys

The thymus is the primary organ responsible for the production of mature TC R alpha/beta T cells. Quantification of a DNA excision circle that is produ ced during TCR rearrangement, termed a signal joint TCR rearrangement excis ion circle (sjTREC) can be used as a measure of thymic function. Here sjTRE C measurement has been applied to two monkey species used as animal models of human disease, rhesus macaques (Asian origin) and sooty mangabeys (Afric an origin). Initial PCR analysis determined that the TCR delta Rec-psi J al pha rearrangement leading to sjTREC formation occurs in both species. Prime rs to a DNA sequence conserved in macaques, mangabeys and humans were used in a quantitative competitive PCR assay to quantify sjTREC. We found that a s in humans, sjTREC in these two monkey species decline with age, sjTREC ar e first generated in thymocytes during the early stages of TCR rearrangemen t. Lymph node CD4(+) and CD8(+) T cells contain more sjTREC than peripheral blood T cell populations, suggesting that recent thymic emigrants home to the lymphoid tissues. The sjTREC level is significantly higher within the p eripheral blood CD4(+) and CD8(+) T cells of mangabeys compared to macaques . Removal of the thymus in four macaques led to a profound decrease in peri pheral blood sjTREC level by 1 year post-thymectomy, indicating the lack of a significant extra-thymic source of peripheral naive T cells in macaques. Our results indicate that production, trafficking, and proliferation of re cent thymic emigrants in these two monkey species represents a useful anima l model system for understanding human immunological disorders.