Evidence for increased T cell turnover and decreased thymic output in HIV infection

The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we invest igated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation , including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected indi viduals undergoing temporary interruption of therapy. We found an inverse a ssociation between increased T cell proliferation with rapid viral recrudes cence and a decrease in TREC levels. However, during early HIV infection, w e found that CD45RO(-)CD27(high) (naive) CD4(+) T cell proliferation did no t increase, despite a loss of TREC within naive CD4(+) T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T c ell homeostasis that underlie the pathogenesis of AIDS.