Dual function of a human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte clone: inhibition of HIV replication by noncytolytic mechanisms and lysis of HIV-infected CD4+ cells.
CD8+ T cells may play a beneficial role in human immunodeficiency virus (HIV)-infected patients by two mechanisms. HIV-specific cytotoxic activity and secretion of a soluble mediator(s) that inhibits HIV replication in vitro. Here we characterized both activities mediated by an HIV p24gag-specific cytotoxic T lymphocyte (CTL) CD8+ clone derived from an HIV-infected patient. When the CTL clone was mixed with HIV-infected autologous CD4+ T cells, viral replication was suppressed. This viral inhibition was observed in heterologous CD4+ T cells and when CD8+ and CD4+ populations were separated by a semipermeable membrane, demonstrating the involvement of a diffusible factor(s). The lysis of autologous HIV-infected T cells was also detected. However, HIV suppression was more efficient when CD4+ and CD8+ T cells shared major histocompatibility complex alleles and were in direct contact. Thus, one and the same CD8+ T cell population can mediate both lysis of HIV-infected targets and nonlytic suppression of HIV replication. These results underline the multiple roles of CD8+ T lymphocytes in the suppression of HIV-infected cells.
Buseyne
F
F
Unité de Virologie et Immunologie Cellulaire, URA CNRS 1157, Institut Pasteur, Paris, France.
Février
M
M
Garcia
S
S
Gougeon
M L
ML
Rivière
Y
Y
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002999:Clone Cells; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D016655:HIV Core Protein p24; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta