Background: Effective amplification of the response of CD4⁺ T-cells depends on both the proliferative capacities of the CD4⁺ T-cells upon antigen stimulation and the immunologic functions of the proliferating cells through the different stages of proliferation.

Methods: Proliferative capacities of the peripheral blood CD4⁺ T-cells from 5 non-HIV infected controls and 6 HIV-infected subjects were studied using an anti-CD3:anti-CD8 bispecific mAb (CD3,8) + IL2 + HAART in an artificial capillary cartridge system. CD3,8 was left in for the first 4 days and HAART was left in for the first 19 days only. Proliferating cells were partially harvested periodically and frozen. The cells from early and late stages of proliferation were thawed together and immunologic assays performed.

Results: CD3,8 redirect cytolysis of CD8⁺ T-cells and led to proliferation of the residual CD4⁺ T-cells by stimulating the TCR in the presence of IL2. In the presence of HAART, CD3,8 + IL2 led to elimination of replication-competent virus presumably by activating the latent virus to lyse the infected cells while preventing new infections from being established. For normal subjects, the number of doubling achieved varied between 17.3 to > 38.1 generations (25.1 mean). For HIV-infected subjects, the number of doubling achieved varied between 10 to 38 (19.7 mean). For 3 subjects whose CD4⁺ T-cell count was ≤ 300, the number of doubling achieved varied between 10 to 16.7 (12.9 mean). The immunologic assays showed similar response between early and late proliferating cells of the same subject though varied greatly between different subjects, including mitogen induced proliferation. As a group, the percentage of cells expressing cytoplasmic cytokines were higher for normal vs HIV-infected subjects for TNFa(46% vs 26%); and IL2(28% vs 7%). The result for IFNg (32% vs 39%) and IL4 (1.9% vs 1.4%) were similar. In contrast, CD4⁺ T-cells from HIV-infected subjects induced greater cytolysis than the CD4⁺ T-cells of normal subjects (51% vs 28%).

Conclusions: CD4⁺ T-cells from both normal HIV-infected subjects can proliferate substantially upon a single period of TCR stimulation, but lower for advanced HIV-infected subjects. CD4⁺ T-cells of both normal and HIV-infected subjects remain immunocompetent upon substantial cell expansion. The CD4⁺ T-cells of HIV-infected have a diminished cytokine producing capacities, but greater cytolytic capacity compared to CD4⁺ T-cells of normal subjects.