Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class ii major histocompatibility complex-restricted antigen-specific T helper clones T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals

Naoki Oyaizu, Narendra Chirmule, Savita G Pahwa

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16 Citations (Scopus)

Abstract

The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal trensduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) α chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.

Original languageEnglish
Pages (from-to)1807-1816
Number of pages10
JournalJournal of Clinical Investigation
Volume89
Issue number6
StatePublished - Dec 1 1992
Externally publishedYes

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CD3 Antigens
CD4 Antigens
Interleukin-2 Receptors
Viral Tumor Antigens
Helper-Inducer T-Lymphocytes
T-Cell Antigen Receptor
Major Histocompatibility Complex
Interleukin-2
Clone Cells
Antigens
Phosphatidylinositols
Hydrolysis
T-Lymphocytes
Messenger RNA
Ionomycin
Inositol Phosphates
Membranes
Genes
Epitopes
Monoclonal Antibodies

Keywords

  • Cytokine receptor regulation
  • Human immunodeficiency virus glycoprotein 120 receptor
  • Lymphoproliferation
  • Signal transduction
  • T cell activation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class ii major histocompatibility complex-restricted antigen-specific T helper clones T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals",
abstract = "The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal trensduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) α chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.",
keywords = "Cytokine receptor regulation, Human immunodeficiency virus glycoprotein 120 receptor, Lymphoproliferation, Signal transduction, T cell activation",
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AU - Oyaizu, Naoki

AU - Chirmule, Narendra

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