Promotion of human T lymphocyte proliferation by IL-4

L. C. Mitchell, L. S. Davis, P. E. Lipsky

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The capacity of human rIL-4 to support the proliferation of mitogen-stimulated T cells directly as well as by increasing IL-2 production or enhancing IL-2 responsiveness was investigated. IL-4 augmented proliferation of T cells stimulated with PHA, Con A, immobilized mAb to the CD3 molecular complex (OKT3), or PMA. IL-4 increased the number of mitogen-stimulated cells entering the cell cycle as well as enhancing ongoing proliferation of mitogen-activated lymphoblasts. Facilitation of initial activation by IL-4 was not inhibited by mAb to the p55 component of the IL-2R, anti-Tac, and, therefore, was not dependent on endogenous IL-2 activity. However, IL-4-mediated enhancement of ongoing T cell proliferation stimulated by PHA or OKT3 was partially but not completely blocked by anti-Tac. Analysis of the supernatants from PHA-stimulated T cell cultures indicated that IL-4 increased the production of IL-2 by mitogen-activated cells. Moreover, IL-4 increased the amount of IL-2 mRNA that accumulated in mitogen-stimulated T cells. In addition, IL-4 markedly augmented IL-2R expression by PHA-stimulated T cells. Although IL-4 promoted ongoing DNA synthesis of mitogen-stimulated T cells in an IL-2-dependent manner, it was also able to sustain their proliferation directly. Thus, IL-4 supported proliferation of PMA-activated T cells in a manner that was not inhibited by anti-Tac. Furthermore, IL-4 could augment proliferation and IL-2R expression of T cells stimulated with PHA in the presence of cyclosporin A, which blocks endogenous cytokine production or anti-Tac. Finally, IL-4 was noted to enhance proliferation of both CD4+ and CD8+ T cell subsets. The results indicate that IL-4 enhances proliferation of mitogen-activated human T cells by a number of mechanisms, including the direct promotion of cell cycle entry and subsequent DNA synthesis, enhanced production of IL-2, and increased responsiveness to IL-2 in part by up-regulation of IL-2R expression.

Original languageEnglish (US)
Pages (from-to)1548-1557
Number of pages10
JournalJournal of Immunology
Volume142
Issue number5
StatePublished - 1989

Fingerprint

Interleukin-4
T-Lymphocytes
Interleukin-2
Mitogens
Muromonab-CD3
Cell Cycle
CD3 Antigens
DNA
T-Lymphocyte Subsets
Cyclosporine
Up-Regulation
Cell Culture Techniques
Cell Count
Cell Proliferation
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Mitchell, L. C., Davis, L. S., & Lipsky, P. E. (1989). Promotion of human T lymphocyte proliferation by IL-4. Journal of Immunology, 142(5), 1548-1557.

Promotion of human T lymphocyte proliferation by IL-4. / Mitchell, L. C.; Davis, L. S.; Lipsky, P. E.

In: Journal of Immunology, Vol. 142, No. 5, 1989, p. 1548-1557.

Research output: Contribution to journalArticle

Mitchell, LC, Davis, LS & Lipsky, PE 1989, 'Promotion of human T lymphocyte proliferation by IL-4', Journal of Immunology, vol. 142, no. 5, pp. 1548-1557.
Mitchell LC, Davis LS, Lipsky PE. Promotion of human T lymphocyte proliferation by IL-4. Journal of Immunology. 1989;142(5):1548-1557.
Mitchell, L. C. ; Davis, L. S. ; Lipsky, P. E. / Promotion of human T lymphocyte proliferation by IL-4. In: Journal of Immunology. 1989 ; Vol. 142, No. 5. pp. 1548-1557.
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