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PMID: 1534818 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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.

The Journal of clinical investigation ·Vol. 89 ·No. 6 ·1992-06-00 ·Pages 1807-16

Oyaizu N, Chirmule N, Pahwa S

Abstract

The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal transduction 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) alpha 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.

MeSH Terms
Antibodies, Monoclonal/immunology Antigens, Differentiation, T-Lymphocyte/immunology Blotting, Northern CD3 Complex CD4 Antigens/physiology Clone Cells Cytokines/metabolism Flow Cytometry Histocompatibility Antigens Class II/immunology Humans Interleukin-2/biosynthesis Kinetics Lymphocyte Activation RNA, Messenger/metabolism Receptors, Antigen, T-Cell/immunology Receptors, Interleukin-2/biosynthesis Signal Transduction T-Lymphocytes, Helper-Inducer/immunology,physiology
Chemicals
Antibodies, Monoclonal Antigens, Differentiation, T-Lymphocyte CD3 Complex CD4 Antigens Cytokines Histocompatibility Antigens Class II Interleukin-2 RNA, Messenger Receptors, Antigen, T-Cell Receptors, Interleukin-2
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Oyaizu N
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030.
Chirmule N
Pahwa S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115785
Published
1992-06-00
Pages
1807-16
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295879
Subset
IM
Grants
NIAID NIH HHS · AI-28281 · United States
NIDA NIH HHS · DA-05161 · United States
External Links
PubMed source DOI: 10.1172/JCI115785 PMC Full Text View journal details
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