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.