Th1 cells specific for HIV-1 gag p24 are less efficient than Th0 cells in supporting HIV replication, and inhibit...

This report provides three lines of evidence to suggest that T-helper type 1 (Th1) and type 0 (Th0) cells could play an opposing role in acquired immune deficiency syndrome (AIDS). Using a panel of Th1 and Th0 clones specific for human immunodeficiency virus-1 (HIV-1) gag p24, derived from seronegative volunteers immunized with gag p24: Ty virus-like particles, a Th1 clone specific for tuberculin (PPD), and a Th0 clone derived by random activation from the same volunteer, we have demonstrated the following differences in the capacity of these clones to regulate the in vitro replication of HIV. (1) Th1 clones were less efficient than Th0 clones in supporting HIV replication, both in their resting state (by 10-1000-fold) and after antigen activation (by five to 100-fold). Furthermore, the infectious titre of HIV recovered from the Th0 population was more than 1000-fold higher than virus from the Th1 population, and the number of HIV-infected Th0 cells was five to 16 times higher than the number of infected Th1 cells. (2) Antigen- or mitogen-activated Th1, but not Th0 clones, inhibited HIV in bystander CEM-4 cells. Th1 cells also inhibited HIV in autologous and allogeneic Th0 cells. The level of inhibition in these experiments ranged from 50% to 100% and was three to 10-fold higher and more sustained in the presence of p24-specific clones compared to the PPD-specific Th1 clone. The capacity of Th1 cells to inhibit HIV in neighbouring cells was also reflected in the reduced replication of HIV in the clones immediately after antigen activation compared to unstimulated cells. Kinetic studies of virus production, cytokine release and proliferation showed that inhibition of HIV was associated with peak cytokine release and preceeded proliferation. (3) The Th1 clones had higher cytolytic potential than the Th0 clones. Therefore, the HIV inhibitory activity of Th1 cells could be partly due to cell to cell killing. These data demonstrate the opposing effects of Th1 and Th0 cells on the in vitro replication of HIV, and suggest that Th1 cells might be important in immunity whereas Th0/Th2 cells might lay a role in promoting disease.