Human CD4+ cytolytic T lymphocyte responses to a human immunodeficiency virus type 1 gp160 subunit vaccine

The development of an effective vaccine against human immunodeficiency virus type 1 (HIV-1) may require immunization protocols that elicit cytolytic T lymphocytes (CTL) in addition to neutralizing antibodies. This report demonstrates that vaccination of 4 HIV-1-seronegative volunteers with a recombinant HIV-1 gp160 vaccine produced in mammalian cells elicited a CTL response in 3. The observed CTL activity was not mediated by classic CD8+ CTL but rather by cells of the CD4+ phenotype. The level of CTL activity varied over time, did not correlate with the proliferative response to gp160, and was not increased by repeated immunization. At the clonal level, the vaccine was shown to elicit a functionally heterogeneous CD4+ T cell response that included clones with antigen-specific, major histocompatibility complex-restricted cytolytic activity. These clones were capable of lysing target cells expressing the HIV-1 env gene and thus might be active against HIV-1-infected cells in vivo.