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PMID: 9120387 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.

The Journal of experimental medicine ·Vol. 185 ·No. 5 ·1997-03-03 ·Pages 817-24

Szabo SJ, Dighe AS, Gubler U, Murphy KM

Abstract

The developmental commitment to a T helper 1 (Th1)- or Th2-type response can significantly influence host immunity to pathogens. Extinction of the IL-12 signaling pathway during early Th2 development provides a mechanism that allows stable phenotype commitment. In this report we demonstrate that extinction of IL-12 signaling in early Th2 cells results from a selective loss of IL-12 receptor (IL-12R) beta 2 subunit expression. To determine the basis for this selective loss, we examined IL-12R beta 2 subunit expression during Th cell development in response to T cell treatment with different cytokines. IL-12R beta 2 is not expressed by naive resting CD4+ T cells, but is induced upon antigen activation through the T cell receptor. Importantly, IL-4 and IFN-gamma were found to significantly modify IL-12 receptor beta 2 expression after T cell activation. IL-4 inhibited IL-12R beta 2 expression leading to the loss of IL-12 signaling, providing an important point of regulation to promote commitment to the Th2 pathway. IFN-gamma treatment of early developing Th2 cells maintained IL-12R beta 2 expression and restored the ability of these cells to functionally respond to IL-12, but did not directly inhibit IL-4 or induce IFN-gamma production. Thus, IFN-gamma may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R beta 2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses.

MeSH Terms
Animals Cell Differentiation DNA-Binding Proteins/metabolism Gene Expression Regulation, Developmental Interferon-gamma/pharmacology Interleukin-12/pharmacology Mice Mice, Inbred BALB C Mice, Transgenic Protein-Tyrosine Kinases/metabolism RNA, Messenger/analysis Receptors, Interleukin/biosynthesis,genetics Receptors, Interleukin-12 STAT4 Transcription Factor Signal Transduction Spleen/cytology T-Lymphocytes, Helper-Inducer/drug effects Th1 Cells/drug effects,metabolism Th2 Cells/drug effects,metabolism Trans-Activators/metabolism
Chemicals
DNA-Binding Proteins RNA, Messenger Receptors, Interleukin Receptors, Interleukin-12 STAT4 Transcription Factor Stat4 protein, mouse Trans-Activators Interleukin-12 Interferon-gamma Protein-Tyrosine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Szabo S J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dighe A S
Gubler U
Murphy K M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.5.817
Published
1997-03-03
Pages
817-24
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196166
Subset
IM
Grants
NIAID NIH HHS · AI34580 · United States
NIAID NIH HHS · AI31238 · United States
NIAID NIH HHS · AI39676 · United States
External Links
PubMed source DOI: 10.1084/jem.185.5.817 PMC Full Text View journal details
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