TH1 CELLS SPECIFIC FOR HIV-1 GAG P24 ARE LESS EFFICIENT THAN TH0 CELLS IN SUPPORTING HIV REPLICATION, AND INHIBIT VIRUS-REPLICATION IN TH0 CELLS

This report provides three lines of evidence to suggest that T-helper type 1 (Th 1) and type 0 (Th0) cells could play an opposing role in ac quired immune deficiency syndrome (AIDS). Using a panel of Th1 and Th0 clones specific for human immunodeficiency virus-1 (HIV-1) gag p24, d erived from seronegative volunteers immunized with gag p24:Ty virus-li ke particles, a Th1 clone specific for tuberculin (PPD), and a Th0 clo ne derived by random activation from the same volunteer, we have demon strated the following differences in the capacity of these clones to r egulate the in vitro replication of HIV. (1) Th1 clones were less effi cient than Th0 clones in supporting HIV replication, both in their res ting 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 t imes higher than the number of infected Th1 cells. (2) Antigen- or mit ogen-activated Th1, but not Th0 clones, inhibited HIV in bystander CEM -4 cells. Th1 cells also inhibited HIV in autologous and allogeneic Th 0 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 pres ence of p24-specifiic clones compared to the PPD-specific Th1 clone. T he 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 stud ies of virus production, cytokine release and proliferation showed tha t inhibition of HIV was associated with peak cytokine release and prec eded proliferation. (3) The Th1 clones had higher cytolytic potential than the Th0 clones. Therefore, the HIV inhibitory activity of Th1 cel ls 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 whe reas Th0/Th2 cells might lay a role in promoting disease.