Intranasal immunization with HIV reverse transcriptase: effect of dose in the induction of helper T cell type 1 and 2 immunity.

HIV reverse transcriptase (RT) is immunologically recognized by the host after natural infection with HIV. To study the immune response to this nonenvelope protein and the effect of the antigen dose and the immunization route on the differential induction of cellular or humoral responses, CB6F1 mice were immunized intranasally with various doses of recombinant RT (0.025-25 microg/dose) in the presence of the mucosal adjuvant cholera toxin (CT). An antigen-specific, dose-dependent, in vitro proliferative response was observed in splenic cells from all mouse groups immunized with RT and CT. Proliferative responses in salivary gland-associated lymph node (SGALN) cells from the same mice were detected only with higher antigen dose immunizations (2.5, 25 microg/dose). IFN-gamma, a Th1-type cytokine, was detected in RT-stimulated culture supernatants from splenic and SGALN cells from all groups of mice immunized with RT and CT in a dose-dependent fashion. IL-4, a Th2-type cytokine, was detected in RT-stimulated culture supernatants from splenic and SGALN cells from mice immunized with higher doses of RT and CT. RT-specific IgG2a, a Th1-type-related antibody, was detected consistently in sera from all animals immunized with RT and CT and was predominant in mice immunized with lower antigen doses (0.025, 0.25 microg/dose). RT-specific IgG1, a Th2-type-related antibody, was detected consistently in mice immunized with higher antigen doses and was predominant in these groups. These studies demonstrate the immunogenicity of recombinant RT and the effect of the antigen dose in the induction of Th1-type and Th2-type immune responses after mucosal immunization.