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Background:  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. We hypothesize that the defective proliferation of HIV-specific CD8⁺ T cells is linked to impairment in CD4⁺ T-cell help, including reduced production of cytokines.

Methods:  To investigate possible mechanisms that might be responsible for the reduced proliferative potential of HIV-specific CD8⁺ T cells, we examined conditions conducive to the proliferation of CD8⁺ T cells in 14 HIV-infected individuals and 7 HIV-uninfected controls using CFSE labeling and flow cytometry techniques. We analyzed data using 2 quantitative measurements:  the percentage of proliferating CD8⁺ T cells, and the maximum number of cell divisions after stimulation. 

Results:  We found that CD8⁺ T cells from HIV-infected and -uninfected subjects proliferated equally well after polyclonal stimulation by phylohemagglutinin A; both groups reached a percentage of proliferating CD8⁺ T cells of 92 to 96% and a maximum number of cell divisions of 5 to 8. However, in HIV-infected subjects, proliferation of HIV- and CMV-specific CD8⁺ T cells was significantly reduced compared with 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. 

Conclusions:  These results are supportive of the hypothesis that the impairment of CD4 helper cells, including reduced IL-2 production, is a contributing factor to the diminished proliferation of CD8⁺ T cells. Our results may have implications for the design of immune modulation strategies in vivo.

Keywords: CD8; Proliferation ; IL-2