CD4+Human Immunodeficiency Virus Type 1 (HIV-1) Envelope-Specific Cytotoxic T Lymphocytes Derived from the Peripheral Blood Cells of an HIV-1-Infected Individual

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Abstract
Virus-specific cytotoxic T lymphocytes (CTL) are frequently of the CD8+ surface phenotype, although CTL of the CD4+ surface phenotype have also been described. Published reports of CTL derived from peripheral blood mononuclear cells (PBMC) of individuals infected with human immunodeficiency virus type 1 (HIV-1) have described primarily cells of the CD8+ surface phenotype. However, CD4+ HIV-1 envelope-specific CTL have been reported after in vitro stimulation with HIV-1 envelope protein of peripheral blood cells obtained from HIV-1-seronegative donors, in peripheral blood cells after vaccination of HIV-1-seronegative persons with HIV-1 envelope proteins, and in cerebrospinal fluid cells of HIV-1-infected individuals. Recently, CD4+ HIV-1 gag-specific CTL were also reported. We now report a patient from whom we derived HIV-1 envelope-specific CTL cell lines of the CD4+ surface phenotype. Our cell culture technique did not employ exogenous viral antigenic stimulation, and may therefore yield cells that more closely reflect those in the underlying populations from which they were derived. These CTL did not appear to have the clear human leukocyte antigen (HLA) class II restriction pattern typically seen in CD4-expressing cells and were not functionally inhibited by anti-CD3 antibody. Further work will be required to define the role of CD4+ CTL in the pathogenesis of HIV-1 disease.