Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8 ⁺ T Cells

Abstract

Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.

Macrophages and HIV-1: dangerous liaisons

“…Seventeen years after the first phenomenological description of -CAF‖, it is becoming increasing clear that no single protein can account for all the complex activities documented in different experimental systems. Indeed, -CAF‖ appears to be constituted by numerous factors (Baier et al, 1995;Cocchi et al, 1995), some of which are still unknown.…”

Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation

“…CD8 + T cells play an important role in viral eradication through their ability to produce various factors to suppress viral replication and to kill virus-infected cells [1][2][3]. Effector CD8 + T cells have the ability to kill target cells through perforin, granzyme, and the Fas ligands [4,5].…”

Preferential transmission and association of the −403 G → A promoter RANTES polymorphism with atopic asthma

“…In this context, RANTES functions as one of the natural ligands for the chemokine receptor CCR5, thereby suppressing in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. 8 The gene that regulates this chemokine (SCYA5, CCL5) is one of several CC cytokine genes clustered on the q-arm of chromosome 17 and is one of several regions that have been shown to be in linkage with asthma. 9 A mutation in position 403 of the promoter region of RANTES gene has been associated with atopic dermatitis, polymyalgia rheumatica and rheumatoid arthritis.…”