Defective CD4+ T cell signaling in murine AIDS

Uncoupling of the T cell receptor complex from PIP2 hydrolysis

Elizabeth Fitzpatrick, Alan M. Kaplan, Donald A. Cohen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

CD4+ T cells from mice with murine AIDS (MAIDS) have been shown to be unable to respond to TCR stimulation as measured by proliferation, IL-2 production, or IL-2R upregulation, although responsiveness was restored with PMA and ionomycin. In this report we have demonstrated that the inability of MAIDS CD4+ T cells to respond to CD3 stimulation was not associated with reduced surface expression of CD3, CD4, or CD28 and could not be overcome by costimulation with anti-CD28 antibody. However, MAIDS CD4+ T cells failed to activate the PIP2 hydrolysis pathway efficiently, resulting in diminished IP3 production and reduced Ca2+ mobilization compared to normal controls. Additionally, TCR signaling in MAIDS resulted in a reduction in the level of tyrosine phosphorylation of some proteins including deficient tyrosine phosphorylation of PLC-γ1, compared to normal CD4+ T cells. These studies suggest that stimulation through the TCR in CD4+ T cells from MAIDS-infected mice is uncoupled from the phosphotidylinositol hydrolysis pathway due to deficient activation of PLC-γ1.

Original languageEnglish (US)
Pages (from-to)176-187
Number of pages12
JournalCellular Immunology
Volume167
Issue number2
DOIs
StatePublished - Feb 1 1996

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Murine Acquired Immunodeficiency Syndrome
T-Cell Antigen Receptor
Hydrolysis
T-Lymphocytes
Tyrosine
Phosphorylation
Ionomycin
Interleukin-2
Anti-Idiotypic Antibodies
Up-Regulation
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Defective CD4+ T cell signaling in murine AIDS : Uncoupling of the T cell receptor complex from PIP2 hydrolysis. / Fitzpatrick, Elizabeth; Kaplan, Alan M.; Cohen, Donald A.

In: Cellular Immunology, Vol. 167, No. 2, 01.02.1996, p. 176-187.

Research output: Contribution to journalArticle

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