T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART)

Abstract

In human immunodeficiency virus (HIV)-1 infection, highly increased T-cell turnover was proposed to cause exhaustion of lymphocyte production and consequently development of AIDS. Here, we investigated cell proliferation, as measured by expression of the Ki-67 nuclear antigen, in peripheral blood CD41 and CD81 lymphocyte subpopulations before and during highly active antiretroviral therapy (HAART). In untreated HIV-1 infection, both the percentage and number of Ki-671 CD41 and CD81 lymphocytes were significantly increased, compared with values obtained from healthy individuals. A more than 10-fold increase in the percentage of dividing naive CD41 T cells in the blood was found when the number of these cells were below 100 per mL.. HAART induced an immediate decline in Ki-67 antigen expression, despite often very low CD41 T-cell numbers, arguing against increased proliferation being a homeostatic response. After approximately 24 weeks of HAART treatment, a transient increase in the number of proliferating cells was seen, but only in the CD41 CD271 memory pool. In the CD81 T-cell compartment, the number of dividing cells was elevated 20- to 25-fold. This increase was most notable in the CD271 CD 45RO1 and CD272 CD45RO1 memory CD81 T-cell pool, corresponding with the degree of expansion of these subsets. Reduction of plasma HIV-RNA load by HAART was accompanied by a decrease in numbers and percentages of dividing cells in all CD81 T-cell subsets. Taken together, our results indicate that peripheral T-cell proliferation is a consequence of generalized immune activation.