Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
A novel role for tumor necrosis factor-alpha in regulating susceptibility of activated CD4+ T cells from human and nonhuman primates for distinct coreceptor using lentiviruses.
J Acquir Immune Defic Syndr. 2000 May 1;24(1):10-22. Unique Identifier : AIDSLINE MED/20334001 Brice GT; Mayne AE; Villinger F; Ansari AA; Department of Pathology and Laboratory Medicine, Emory University; School of Medicine, Atlanta, Georgia 30322, USA.
Abstract:
Although CD4+ T-cell activation has long been shown to promote infection and replication of simian immunodeficiency virus (SIV) and HIV, recent studies have documented that not all activated CD4+ T cells from human and nonhuman primates are susceptible to infection with HIV/SIV, respectively. Activation of CD4+ T cells with anti-CD3 + anti-CD28 conjugated beads led to induction of a state of anti-viral resistance to infection with strains of viruses that primarily use CCR5 as a coreceptor. The studies reported herein were designed to address the mechanism by which anti-CD3 + anti-CD28-induced stimulation in turn induced antiviral resistance. Results of these studies show that the anti-viral resistance induced by activation of CD4+ T cells with anti-CD3 + anti-CD28 is primarily conferred by the synthesis of tumor necrosis factor-alpha (TNF-alpha), and highlight a unique regulatory role for TNF-alpha in regulating synthesis of MIP-1alpha, MIP-1beta, and regulated-on-activation normal T-expressed and secreted cells, which contributes to this state of antiviral resistance to R5-tropic strains of HIV/SIV. However, while TNF-alpha has a protective role in antiviral resistance of activated CD4+ T cells to R5-tropic viruses, it enhances CXCR4 expression of CD4+ T cells and mediates increased susceptibility to infection with X4-tropic strains of HIV and recombinant SIVs. The results of the studies reported herein also suggest that it is not the Th1 v/s Th2 cytokine profile but the mode of CD4+ T-cell activation that dictates the synthesis of distinct cytokines which regulate the expression of chemokines and chemokine receptors which in turn regulate and confer susceptibility/resistance to R5 v/s X4-tropic HIV and SIV.
Keywords: JOURNAL ARTICLE Adult Animal Antigens, CD28/IMMUNOLOGY Antigens, CD3/IMMUNOLOGY Cells, Cultured CD4-Positive T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY/*VIROLOGY Human HIV-1/GROWTH & DEVELOPMENT/*IMMUNOLOGY Lentivirus/GROWTH & DEVELOPMENT/IMMUNOLOGY Lymphocyte Transformation/*IMMUNOLOGY Macaca mulatta Macrophage Inflammatory Protein-1/BIOSYNTHESIS Neutralization Tests Primates Receptors, CXCR4/*BIOSYNTHESIS RANTES/BIOSYNTHESIS Support, U.S. Gov't, P.H.S. SIV/GROWTH & DEVELOPMENT/*IMMUNOLOGY Tumor Necrosis Factor/*IMMUNOLOGY 001030
A00A1057
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
