T cell regeneration in HIV-infected subjects under highly active antiretroviral therapy (Review)

The initial idea that high amounts of cytopathic virus produced everyday can drive high CD4(+) T cell production seemed logical and explained the progressive CD4(+) T cell depletion observed in HIV-infected subjects. It was hypothesized that the CD4(+) T lymphocyte production was increased up to 70-ford in HIV-infected subjects. Determination of the CD4(+) T cell production was based on the kinetics of CD4(+) T cell recovery following initiation of highly active antiretroviral therapy (HAART). However, this analysis is limited by: i) the assumption that blood CD4(+) T cells are representative of the lymph node T cells; and ii) the lack of estimates of CD4(+) T lymphocyte turnover in healthy HIV-negative subjects. Several immunologists have expressed caution regarding the assumptions used in modeling CD4(+) T cell dynamics. Recent findings clearly show that blood is not representative of lymphoid tissues and invalidate the conclusion of high CD4 turnover drawn from blood studies on HIV-infected subjects. Indeed, when blood and lymph node compartments are considered together, we find that HIV-infected subjects naive to antiretroviral have similar or lower CD4(+) T cell production, as compared to healthy subjects. This observation suggests an impaired T cell renewal capacity in HIV-1 infected patients.