Abstract
Recent studies indicate that a defective proliferative response of HIV‐specific CD8+ T cells is associated with the lack of virologic control in chronic HIV infection in humans. The possible mechanisms that might be responsible for the reduced proliferative potential of HIV‐specific CD8+ T cells and conditions conducive to the proliferation of CD8+ T cells were examined in 14 HIV‐infected individuals and 7 HIV‐uninfected controls using CFSE labeling and flow cytometry techniques, and analyzed data using 2 quantitative measurements: the percentages of proliferating CD8+ T cells (Tp), and the maximum number of cell divisions (Dm) after stimulation. It was found that CD8+ T cells from HIV‐infected and ‐uninfected subjects proliferated equally well after polyclonal stimulation by phylohemagglutinin A (PHA); both groups reached a Tp of 92%–96% and a Dm of 5–8. However, in HIV‐infected subjects, proliferation of HIV‐ and CMV‐specific CD8+ T cells was significantly reduced compared to proliferation of CMV‐ specific CD8+ T cells from HIV‐uninfected subjects. These defective proliferative responses of HIV‐ and CMV‐specific CD8+ T cells were restored by the addition of IL‐2 at the time of stimulation. These results may have implications for the design of immune modulation strategies in vivo. J. Med. Virol. 78:1147–1157, 2006. © 2006 Wiley‐Liss, Inc.