CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells

Seetha M Lakshmi Tamma, Narendra Chirmule, Hirosuka Yagura, Naoki Oyaizu, Vaniambadi Kalyanaraman, Savita G Pahwa

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

CD4 molecules are the primary receptors for human immunodeficiency virus (HIV) and bind the envelope glycoprotein gp120 of HIV with high-affinity. We have previously shown that cross-linking of CD4 molecules (CD4XL) in normal peripheral blood mononuclear cells (PBMC) results in secretion of cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), but not of interleukin-2 (IL-2) or IL-4. To investigate the intracellular signaling events associated with CD4-gp120 interaction, we incubated CD4+ T cells from peripheral blood of HIV-negative healthy donors with HIV envelope protein gp160 alone or performed CD4XL with gp160 and anti-gp160 antibody. This procedure resulted in tyrosine phosphorylation of intracellular substrates p59(fyn), zap 70, and p95(vav) and also led to ras activation, as assessed by conversion of rasGDP to rasGTP. The role of ras in CD4 signaling was further investigated using CD4+ Jurkat cells transfected with a dominant negative ras mutant. CD4+ T cells expressing dn-ras secreted significantly reduced levels of TNF-α in response to CD4XL. These studies indicate that interaction of HIV gp160 with CD4 molecules activates the ras pathway in T calls, which may result in the cells becoming unresponsive to subsequent stimulation.

Original languageEnglish
Pages (from-to)1588-1593
Number of pages6
JournalBlood
Volume90
Issue number4
StatePublished - Aug 15 1997
Externally publishedYes

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T-cells
Viruses
CD4 Antigens
Tumor Necrosis Factor-alpha
Chemical activation
HIV
T-Lymphocytes
Human Immunodeficiency Virus env Gene Products
Blood
Phosphorylation
Jurkat Cells
Interleukin-4
Interferons
Interleukin-2
Tyrosine
Anti-Idiotypic Antibodies
Blood Cells
Glycoproteins
Cytokines
Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

Tamma, S. M. L., Chirmule, N., Yagura, H., Oyaizu, N., Kalyanaraman, V., & Pahwa, S. G. (1997). CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells. Blood, 90(4), 1588-1593.

CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells. / Tamma, Seetha M Lakshmi; Chirmule, Narendra; Yagura, Hirosuka; Oyaizu, Naoki; Kalyanaraman, Vaniambadi; Pahwa, Savita G.

In: Blood, Vol. 90, No. 4, 15.08.1997, p. 1588-1593.

Research output: Contribution to journalArticle

Tamma, SML, Chirmule, N, Yagura, H, Oyaizu, N, Kalyanaraman, V & Pahwa, SG 1997, 'CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells', Blood, vol. 90, no. 4, pp. 1588-1593.
Tamma SML, Chirmule N, Yagura H, Oyaizu N, Kalyanaraman V, Pahwa SG. CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells. Blood. 1997 Aug 15;90(4):1588-1593.
Tamma, Seetha M Lakshmi ; Chirmule, Narendra ; Yagura, Hirosuka ; Oyaizu, Naoki ; Kalyanaraman, Vaniambadi ; Pahwa, Savita G. / CD4 cross-linking (CD4XL) induces ras activation and tumor necrosis factor-α secretion in CD4+ T cells. In: Blood. 1997 ; Vol. 90, No. 4. pp. 1588-1593.
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