Lymphocyte turnover in HIV-1 infection and the role of the thymus in SIV infection

We investigated the dynamics of lymphocyte turnover in normal subjects as well as in HIV-1-infected patients using a novel labeling technique based on the administration of deuterium-containing glucose. A new mathematical model was also used to interpret the results. This approach provided direct determination of lymphocyte proliferation and death rates. We believe our findings convincingly demonstrate the increased turnover (3-6 fold) of both CD4 and CD8 lymphocytes in HIV-1 infection. Furthermore, we also noted that the heightened T-cell turnover reverted toward normal upon effective combination antiretroviral therapy. Collectively, these data show that the lymphocyte depletion seen in AIDS is not a consequence of a T-cell regenerative failure.We have also assessed the role of thymus in contributing to T lymphocyte homeostasis with and without SIV infection. Upon thymectomy in rhesus macaques, we noted a very gradual decline in the number of recent thymic emigrants as measured by the number of T-cell receptor excision circles. These results suggest that the normal thymic output in monkeys is small, and that recent thymic emigrants typically have a prolonged lifespan. We have also found relatively little impact of thymectomy on the outcome of SIV infection. Again, these findings indicate that thymus does not play a major role in the lymphocyte depletion observed in SIV or HIV infection.