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

Abstract

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 monocyte͞macrophages (M͞M) has not been fully delineated. To investigate whether a CD8؉ T-cell-derived soluble factor(s) can also suppress HIV infection in the M͞M 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 ␤-chemokines. We demonstrate that: (i) CD8؉ T-cell supernatants did, but ␤-chemokines did not, suppress HIV replication in the M͞M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inf lammatory protein 1␣ (MIP-1␣) and MIP-1␤ did not, whereas antibodies to interleukin 10, interleukin 13, interferon ␣, or interferon ␥ modestly reduced anti-HIV activity of the CD8 ؉ T-cell supernatants; and (iii) the CD8 ؉ T-cell supernatants did, but ␤-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␣, and MIP-1␤ do not account for the entire scope of CD8 ؉ T-cell-derived HIV-suppressor factors.

Octamer Transcription Factors Up-regulate the Expression of CCR5, a Coreceptor for HIV-1 Entry

“…Cells-Peripheral blood mononuclear cells were obtained from healthy volunteers (Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health and Red Cross Blood Center in Nagasaki Prefecture, Japan), and CD4 ϩ T cells were isolated as described previously (25). Where indicated, CD4 ϩ T cells were stimulated with phorbol 12-myristate 13-acetate (PMA) (1 M) plus ionomycin (1 M) or anti-CD3 plus anti-CD28 antibodies immobilized by immunomagnetic beads for 8 h. CCR5-expressing PM1 lymphoid cells were propagated as described previously (19).…”

Prothymosin-α inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction

“…In an effort to identify host proteins that protect macrophages against HIV-1 infection, we reported a strategy to screen for postentry HIV-1 inhibitors from CD8 + T cell conditioned medium by using supernatants of herpes virus saimiri-transformed CD8 + T cells (1). Although several molecules with anti-HIV-1 activity, including the β-chemokines RANTES, MIP-1α and β (2), and macrophage-derived chemokine (MDC) (3), have been found in CD8 + T cell supernatants, these do not account for the full spectrum of soluble anti-HIV-1 activity (1,(4)(5)(6). We reported the isolation and identification of prothymosin-α (ProTα) from a fraction derived from the CD8 + T cell culture medium and demonstrated that this protein has potent postentry HIV-1-inhibitory activity in macrophages (7).…”

High Beta-Chemokine Expression Levels in Lymphoid Tissues of Simian/Human Immunodeficiency Virus 89.6-Vaccinated Rhesus Macaques Are Associated with Uncontrolled Replication of Simian Immunodeficiency Virus Challenge Inoculum

“…Beta-chemokines are produced at sites of inflammation, where they are involved in the recruitment of T cells and macrophages (13,33,36,44), but the net effect of beta-chemokine secretion by CD8 ϩ T cells in lentiviral infections is unclear. Some studies have shown that members of the beta-chemokine family can block HIV and SIV replication (12,20), but others have concluded that CD8 ϩ -Tcell-mediated inhibition of viral replication in vitro is due to soluble factors other than beta-chemokines (10,11,31,35).…”