AN HIV-1 ENVELOPE PROTEIN VACCINE ELICITS A FUNCTIONALLY COMPLEX HUMAN CD4-CELL RESPONSE THAT INCLUDES CYTOLYTIC T-LYMPHOCYTES( T)

T cell responses play a critical role in host defense against viral in fection. Therefore, the functional properties of HIV-1-specific human T cells induced by an experimental AIDS vaccine were analyzed in detai l at the clonal level. Seronegative human volunteers were immunized wi th a purified recombinant form of the HIV-1 envelope glycoprotein gp16 0 in a phase I vaccine trial. In a subset of gp160 recipients, this va ccine was shown to elicit a virus-specific CTL response. Antibody bloc king and single cell cloning experiments demonstrated that the vaccine -induced cytoltyic activity was mediated by CD4+, MHC class II-restric ted T cells. Because little is known about the regulation of CD4+ CTL in any system, a detailed analysis of CTL responses in vaccinees was c arried out. Longitudinal and cross-sectional studies revealed that the CD4+ CTL response was regulated in a complex manner and was not clear ly correlated with MHC class II genotype, Ag dose, or number of immuni zations. Cloning studies were carried out to determine what fraction o f the vaccine-induced T cells were cytolytic and to examine patterns o f cytokine production by vaccine-induced T cells. These experiments de monstrated that, for some vaccinees, CD4+ CTL dominated the in vitro-T cell response to gp160 at certain time points. The level of cytolytic activity, which was a stable property of individual clones, varied am ong clones over a wide and continuous range. Analysis of cytokine secr etion by gp160-specific CD4+ T cell clones revealed Th0-, Th1-, and Th 2-like patterns, with CD4+ CTL clones showing Th0- or Th1-like pattern s. Interestingly, many Th0- and Th1-like CTL clones produced very litt le IL-2, a finding that may explain the complicated regulation of this response. These results illustrate the complex nature of the human T cell response to subunit vaccines consisting of purified recombinant v iral proteins.