Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus

Narendra Chirmule, Vaniambadi S. Kalyanaraman, Naoki Oyaizu, Herbert B. Slade, Savita G Pahwa

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

We investigated mechanisms by which the soluble native envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1) suppresses antigen-driven T cell responses. For this study, exogenous interleukin-2 (IL-2)-independent, antigen-specific, CD4 positive, human T cell clones were developed by cyclic restimulation with soluble tetanus toxoid antigen. In the presence of soluble antigen and antigen-presenting cells (APC), T-cell clones proliferated and secreted IL-2. Purified gp120 suppressed the proliferative responses of the T-cell clones with concomitant suppression of IL-2 secretion; proliferative responses of CD8+ T cells preincubated with gp120 were not inhibited. A short pulse of 20 minutes with gp120 was sufficient to inhibit the proliferative response of the T-cell clones. Anti-CD3 monoclonal antibody (MoAb)-driven proliferation of the T-cell clones was also suppressed by gp120, but responses elicited by mitogens, phorbol myristate acetate (PMA) plus calcium ionophore, ionomycin, anti-CD2 MoAbs, and a combination of anti-CD3 plus anti-CD28 MoAb driven responses remained unaffected Investigation of signal transduction events showed that antigen-driven early activation signals via translocation of protein kinase C (PKC), increase in intracellular inositol phosphates, and increase in intracellular calcium were suppressed in gp120 pretreated, tetanus toxoid antigen-stimulated T-cell clones. One mechanism of immune suppression by gp120 may involve interference with the initiation of signal transduction through the T-cell receptor complex.

Original languageEnglish
Pages (from-to)152-159
Number of pages8
JournalBlood
Volume75
Issue number1
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

T-cells
Tetanus
Viruses
Glycoproteins
Clone Cells
HIV
T-Lymphocytes
Antigens
Interleukin-2
Signal transduction
Tetanus Toxoid
HIV-1
Signal Transduction
Monoclonal Antibodies
CD4 Antigens
Ionomycin
Inositol Phosphates
Calcium Ionophores
Tetradecanoylphorbol Acetate
Antigen-Presenting Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. / Chirmule, Narendra; Kalyanaraman, Vaniambadi S.; Oyaizu, Naoki; Slade, Herbert B.; Pahwa, Savita G.

In: Blood, Vol. 75, No. 1, 01.01.1990, p. 152-159.

Research output: Contribution to journalArticle

Chirmule, Narendra ; Kalyanaraman, Vaniambadi S. ; Oyaizu, Naoki ; Slade, Herbert B. ; Pahwa, Savita G. / Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. In: Blood. 1990 ; Vol. 75, No. 1. pp. 152-159.
@article{7065bd011da948699f59fda4ed9737e2,
title = "Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus",
abstract = "We investigated mechanisms by which the soluble native envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1) suppresses antigen-driven T cell responses. For this study, exogenous interleukin-2 (IL-2)-independent, antigen-specific, CD4 positive, human T cell clones were developed by cyclic restimulation with soluble tetanus toxoid antigen. In the presence of soluble antigen and antigen-presenting cells (APC), T-cell clones proliferated and secreted IL-2. Purified gp120 suppressed the proliferative responses of the T-cell clones with concomitant suppression of IL-2 secretion; proliferative responses of CD8+ T cells preincubated with gp120 were not inhibited. A short pulse of 20 minutes with gp120 was sufficient to inhibit the proliferative response of the T-cell clones. Anti-CD3 monoclonal antibody (MoAb)-driven proliferation of the T-cell clones was also suppressed by gp120, but responses elicited by mitogens, phorbol myristate acetate (PMA) plus calcium ionophore, ionomycin, anti-CD2 MoAbs, and a combination of anti-CD3 plus anti-CD28 MoAb driven responses remained unaffected Investigation of signal transduction events showed that antigen-driven early activation signals via translocation of protein kinase C (PKC), increase in intracellular inositol phosphates, and increase in intracellular calcium were suppressed in gp120 pretreated, tetanus toxoid antigen-stimulated T-cell clones. One mechanism of immune suppression by gp120 may involve interference with the initiation of signal transduction through the T-cell receptor complex.",
author = "Narendra Chirmule and Kalyanaraman, {Vaniambadi S.} and Naoki Oyaizu and Slade, {Herbert B.} and Pahwa, {Savita G}",
year = "1990",
month = "1",
day = "1",
language = "English",
volume = "75",
pages = "152--159",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus

AU - Chirmule, Narendra

AU - Kalyanaraman, Vaniambadi S.

AU - Oyaizu, Naoki

AU - Slade, Herbert B.

AU - Pahwa, Savita G

PY - 1990/1/1

Y1 - 1990/1/1

N2 - We investigated mechanisms by which the soluble native envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1) suppresses antigen-driven T cell responses. For this study, exogenous interleukin-2 (IL-2)-independent, antigen-specific, CD4 positive, human T cell clones were developed by cyclic restimulation with soluble tetanus toxoid antigen. In the presence of soluble antigen and antigen-presenting cells (APC), T-cell clones proliferated and secreted IL-2. Purified gp120 suppressed the proliferative responses of the T-cell clones with concomitant suppression of IL-2 secretion; proliferative responses of CD8+ T cells preincubated with gp120 were not inhibited. A short pulse of 20 minutes with gp120 was sufficient to inhibit the proliferative response of the T-cell clones. Anti-CD3 monoclonal antibody (MoAb)-driven proliferation of the T-cell clones was also suppressed by gp120, but responses elicited by mitogens, phorbol myristate acetate (PMA) plus calcium ionophore, ionomycin, anti-CD2 MoAbs, and a combination of anti-CD3 plus anti-CD28 MoAb driven responses remained unaffected Investigation of signal transduction events showed that antigen-driven early activation signals via translocation of protein kinase C (PKC), increase in intracellular inositol phosphates, and increase in intracellular calcium were suppressed in gp120 pretreated, tetanus toxoid antigen-stimulated T-cell clones. One mechanism of immune suppression by gp120 may involve interference with the initiation of signal transduction through the T-cell receptor complex.

AB - We investigated mechanisms by which the soluble native envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1) suppresses antigen-driven T cell responses. For this study, exogenous interleukin-2 (IL-2)-independent, antigen-specific, CD4 positive, human T cell clones were developed by cyclic restimulation with soluble tetanus toxoid antigen. In the presence of soluble antigen and antigen-presenting cells (APC), T-cell clones proliferated and secreted IL-2. Purified gp120 suppressed the proliferative responses of the T-cell clones with concomitant suppression of IL-2 secretion; proliferative responses of CD8+ T cells preincubated with gp120 were not inhibited. A short pulse of 20 minutes with gp120 was sufficient to inhibit the proliferative response of the T-cell clones. Anti-CD3 monoclonal antibody (MoAb)-driven proliferation of the T-cell clones was also suppressed by gp120, but responses elicited by mitogens, phorbol myristate acetate (PMA) plus calcium ionophore, ionomycin, anti-CD2 MoAbs, and a combination of anti-CD3 plus anti-CD28 MoAb driven responses remained unaffected Investigation of signal transduction events showed that antigen-driven early activation signals via translocation of protein kinase C (PKC), increase in intracellular inositol phosphates, and increase in intracellular calcium were suppressed in gp120 pretreated, tetanus toxoid antigen-stimulated T-cell clones. One mechanism of immune suppression by gp120 may involve interference with the initiation of signal transduction through the T-cell receptor complex.

UR - http://www.scopus.com/inward/record.url?scp=0025058349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025058349&partnerID=8YFLogxK

M3 - Article

C2 - 1967213

AN - SCOPUS:0025058349

VL - 75

SP - 152

EP - 159

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -