T cell proliferation and apoptosis in HIV-1-infected lymphoid tissue: Impact of highly active antiretroviral therapy

T cell turnover was studied in situ in tonsillar lymphoid tissue (LT) from HIV-1-infected individuals during 48 weeks of highly active antiretroviral therapy (HAART) and compared to that of HIV-1-negative controls. Prior to t herapy, CD4 cell proliferation (%CD4(+) Ki67(+)) and apoptosis (%CD4(+) TUN EL+) were increased in HIV-1-infected LT and both parameters correlated wit h tonsillar viral load. CD8 cell proliferation (%CD8(+) Ki67(+)) was increa sed 4- to 10-fold, mainly in the germinal centers. Apoptotic CD8(+) T cell levels (%CD8(+) TUNEL+) were raised preferentially in the tonsillar T cell zone. The frequency of CD8(+) Ki67(+) and CD8(+) TUNEL+ T cells correlated with tonsillar viral load and with the fraction of CD8(+) T cells expressin g activation markers. During HAART, CD4 cell turnover normalized while CD8 cell turnover was dramatically reduced. However, low level viral replicatio n concomitant with slightly elevated levels of CD8 cell turnover indicated a persistent cellular immune response in LT. In conclusion, enhanced T cell turnover may reflect effector cells related to HIV-1 infection. (C) 2001 A cademic Press.