CD8(+) T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1 alpha, an MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages

It has been demonstrated that CD8(+) T cells produce a soluble factor(s) that suppresses human immunodeficiency virus (HIV) replication in CD4(+) T cells. The role of soluble factors in the suppression of HIV replication in monocyte/macrophages (M/M) has not been fully delineated. To investigate whether a CD8(+) T-cell-derived soluble factor(s) can also suppress HIV infection in the M/M system, primary macrophages were infected with the macrophage tropic HIV-1 strain Ba-L. CD8(+) T-cell-depleted peripheral blood mononuclear cells were also infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected macrophage cell line U1 was also determined in the presence of CD8(+) T-cell supernatants or beta-chemokines. We demonstrate that: (i) CD8(+) T-cell supernatants did, but beta-chemokines did not, suppress HIV replication in the M/M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta did not, whereas antibodies to interleukin 10, interleukin 13, interferon alpha, or interferon gamma modestly reduced anti-HIV activity of the CD8(+) T-cell supernatants; and (iii) the CD8(+) T-cell supernatants did, but beta-chemokines did not, suppress HIV-1 IIIB replication in peripheral blood mononuclear cells as well as HIV expression in U1 cells. These results suggest that HIV-suppressor activity of CD8(+) T cells is a multifactorial phenomenon, and that RANTES, MIP-1 alpha, and MIP-1 beta do not account for the entire scope of CD8(+) T-cell-derived HIV-suppressor factors.