Role of class I major histocompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 replication by CD8(+) T lymphocytes

CD8(+) T lymphocytes of asymptomatic human immunodeficiency virus type 1 (H IV-1) carriers (ACs) are capable of suppressing HIV-1 replication in CD4(+) peripheral blood mononuclear cells (PBMC) by a variety of known and unknow n mechanisms. In the present study, cell contact-dependent, major histocomp atibility complex type I (MHC I)-unrestricted, CD8(+) cell-mediated suppres sion of HIV-1 LAI replication was detected. CD8+ PBMC of ACs suppressed HIV -1 replication more efficiently in MHC I-matched CD4(+) PBMC than in mismat ched cells. However, even when MHC I was totally mismatched, CD8(+) cells s till suppressed replication to a considerable extent in CD4(+) PBMC, This M HC I-unrestricted, CD8(+) cell-mediated HIV-1 suppression required cell con tact and was not effective against cells of the established T cell line ILT -KK, In contrast, MHC I-restricted HIV-1 suppression by CD8(+) T cells was detected when ILT-KK cells were used as a target. By using these systems, w e examined MHC I-restricted and -unrestricted suppressive activities of CD8 (+) cells in various donors in more detail. Although both types of CD8(+) c ell-mediated HIV-1 suppression diminished at the advanced stage of the infe ction, MHC I-unrestricted suppression diminished earlier than MHC I-restric ted suppression, in parallel with the decline in CD4(+) T cells. These resu lts suggest that suppression by the MHC I-restricted mechanism alone may fa il to protect against CD4(+) T-cell loss at the late stage of infection.