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PMID: 1824637 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interleukin 4 expressed in situ selectively alters thymocyte development.

The Journal of experimental medicine ·Vol. 173 ·No. 1 ·1991-01-01 ·Pages 89-100

Lewis DB, Yu CC, Forbush KA, Carpenter J, Sato TA, Grossman A, Liggitt DH, Perlmutter RM

Abstract

Using a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL-4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization of calcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8- and CD4-CD8+) thymocytes and peripheral T cells exhibit decreased TCR-mediated calcium mobilization. The development of CD4-CD8+ thymocytes is significantly perturbed by IL-4 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4-CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers of B cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that IL-4 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, Differentiation, T-Lymphocyte/analysis B-Lymphocytes/physiology CD4 Antigens/analysis CD8 Antigens Immunoglobulin Isotypes/blood Interleukin-4/physiology Lymphocyte Activation Mast Cells/physiology Mice Mice, Transgenic Organ Specificity Phenotype Receptors, Antigen, T-Cell/biosynthesis Receptors, Antigen, T-Cell, alpha-beta Recombinant Proteins/metabolism T-Lymphocytes/cytology,immunology Thymus Gland/cytology
Chemicals
Antibodies, Monoclonal Antigens, Differentiation, T-Lymphocyte CD4 Antigens CD8 Antigens Immunoglobulin Isotypes Receptors, Antigen, T-Cell Receptors, Antigen, T-Cell, alpha-beta Recombinant Proteins Interleukin-4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lewis D B
Department of Pediatrics, University of Washington, Seattle 98195.
Yu C C
Forbush K A
Carpenter J
Sato T A
Grossman A
Liggitt D H
Perlmutter R M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.173.1.89
Published
1991-01-01
Pages
89-100
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118750
Subset
IM
Grants
NIAID NIH HHS · AI/HD 26940 · United States
External Links
PubMed source DOI: 10.1084/jem.173.1.89 PMC Full Text View journal details
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