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PMID: 8760801 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

The Journal of experimental medicine ·Vol. 184 ·No. 2 ·1996-08-01 ·Pages 473-83

Sornasse T, Larenas PV, Davis KA, de Vries JE, Yssel H

Abstract

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

MeSH Terms
CD4-Positive T-Lymphocytes/cytology,immunology Cell Differentiation/drug effects Cell Division/drug effects Cytokines/biosynthesis Fetal Blood Flow Cytometry Humans Interferon-gamma/pharmacology Interleukin-12/pharmacology Interleukin-13/pharmacology Interleukin-4/pharmacology Recombinant Proteins Th1 Cells/cytology,immunology Th2 Cells/cytology,immunology Time Factors
Chemicals
Cytokines Interleukin-13 Recombinant Proteins Interleukin-12 Interleukin-4 Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sornasse T
Department of Human Immunology, DNAX Research Institute, Palo Alto, California 94304, USA.
Larenas P V
Davis K A
de Vries J E
Yssel H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.2.473
Published
1996-08-01
Pages
473-83
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192741
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.184.2.473 PMC Full Text View journal details
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