CONTACT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED AND UNINFECTED CD4(+) T-LYMPHOCYTES IS HIGHLY CYTOLYTIC FOR BOTH CELLS

Individuals infected with the human immunodeficiency virus (HIV) experience a marked loss of CD4(+) T lymphocytes, leading to fatal immunodeficiency, The mechanisms causing the depletion of these cells are not yet understood, In this study, we observed that CD4(+) T lymphocytes from HIV type 1 (HIV-1)-infected and uninfected individuals rapidly lysed B lymphoblasts expressing the HIV-1 envelope glycoprotein on the cell surface and Jurkat cells expressing the complete virus. Contact of uninfected CD4(+) T cells with envelope glycoprotein-expressing cells also resulted in the lysis of the uninfected CD4(+) T cells. Cytolysis did not require priming or in vitro stimulation of the CD4(+) T cells and was not restricted by major histocompatibility complex molecules. Cytotoxicity was inhibited by soluble CD4 and anti-CD4 monoclonal antibodies that block binding of CD4 to gp120. In addition, neutralizing anti-CD4 and anti-gp120 monoclonal antibodies which block postbinding membrane fusion events and syncytium formation also inhibited cell lysis, suggesting that identical mechanisms in HIV-infected cultures underlie cell-cell fusion and the cytolysis observed. However, cytotoxicity was not always accompanied by the formation of visible syncytia. Rapid cell lysis after contact of uninfected and HIV-1-infected CD4(+) T cells may explain CD4(+) T-cell depletion in the absence of detectable syncytia in infected individuals, Moreover, because of its vigor, lysis of envelope-expressing targets by contact ,vith unprimed CD4(+) T lymphocytes may at first glance resemble antigen-specific immune responses and should be excluded when cytotoxic T-lymphocyte responses in infected individuals and vaccinees are evaluated.