HLA compatibility requirements for CD8(+)-T-cell-mediated suppression of human immunodeficiency virus replication.
CD8(+) T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in cultured CD4(+) cells by a noncytotoxic mechanism. Efficient suppression of HIV replication (>90% reduction) does not require HLA class I or class II histocompatibility between the effector CD8(+) T cells and the infected target CD4(+) T cells. However, maximal control of HIV production occurs when the CD8(+) effector cells and CD4(+) target cells are syngeneic. In some cases, more than 20-fold fewer syngeneic CD8(+) T cells were required to achieve the same degree of HIV inhibition as HLA-mismatched CD8(+) T cells. The increased antiviral activity seen in the syngeneic setting did not map exclusively to either the HLA class I or class II locus. These findings suggest that genetic compatibility (potentially, but not necessarily, at the HLA class I and class II loci) regulates CD8(+) T-cell noncytotoxic antiviral activity against infected CD4(+) T cells.
Mackewicz
C E
CE
Department of Medicine, Department of Surgery, School of Medicine, University of California, San Francisco, San Francisco, California 94143-1270, USA.
Garovoy
M R
MR
Levy
J A
JA
D019264:Adoptive Transfer; D000998:Antiviral Agents / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D066298:In Vitro Techniques; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D000998:Antiviral Agents; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II