Signals Transduced through the CD4 Molecule Interfere with TCR/CD3-Mediated Ras Activation Leading to T Cell Anergy/Apoptosis

It has been previously demonstrated that the occupancy of CD4 molecules by the HIV-1 envelope glycoprotein gp120 results in marked inhibition of T cell receptor–CD3 complex (TCR/CD3) activation-induced IL-2 secretion. To elucidate the mechanism of inhibitory effects of gp160 on T cell signaling, we...

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Bibliographic Details
Published in:Clinical immunology and immunopathology 1997-11, Vol.85 (2), p.195-201
Main Authors: Tamma, Seetha M.Lakshmi, Chirmule, Narendra, McCloskey, Thomas W., Oyaizu, Naoki, Kalyanaraman, V.S., Pahwa, Savita
Format: Article
Language:English
Subjects:
AIDS/HIV
Apoptosis - physiology
Biological and medical sciences
CD3 Complex - physiology
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
fas Receptor - biosynthesis
Gene Expression Regulation
Genes, ras - genetics
HIV Envelope Protein gp120 - pharmacology
HIV Envelope Protein gp160 - pharmacology
HIV-1
Human viral diseases
Humans
Infectious diseases
Interleukin-2 - metabolism
Lymphocyte Activation - drug effects
Medical sciences
Phosphorylation - drug effects
Protein-Tyrosine Kinases - metabolism
Receptors, Antigen, T-Cell - physiology
Signal Transduction - physiology
Tumor Necrosis Factor-alpha - analysis
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Summary:It has been previously demonstrated that the occupancy of CD4 molecules by the HIV-1 envelope glycoprotein gp120 results in marked inhibition of T cell receptor–CD3 complex (TCR/CD3) activation-induced IL-2 secretion. To elucidate the mechanism of inhibitory effects of gp160 on T cell signaling, we have investigated the intracellular biochemical events and biological output in response to anti-CD3 mAb activation of purified peripheral blood CD4+T cells from healthy donors with and without prior exposure to HIV-1 gp160. Pretreatment with gp160 resulted in marked inhibition of tyrosine phosphorylation of p59fyn, PLC-γ1, ras activation, and TNF-α secretion in anti-CD3 mAb activated CD4+ T cells, and a subset of CD4+cells underwent activation-induced cell death. The data presented here provide insight into the mechanism by which the interaction of HIV-1 envelope glycoproteins with CD4 molecules may alter TCR/CD3-activation-induced signal transduction resulting in anergy and apoptosis with consequent functional deficiency of CD4+T cells.
ISSN:0090-1229
1090-2341
DOI:10.1006/clin.1997.4424