Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses

Cecile King, Regula Mueller Hoenger, Mary Malo Cleary, Kaja Murali-Krishna, Rafi Ahmed, Ernest King, Nora E Sarvetnick

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has remained unexplained. Here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic pre-cursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. The molecular basis for this regulation is the alteration of the expression ratio of the costimulatory ligands B7.1/B7.2 on dendritic cells. Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualitative differences in T-cell responses, providing the basis for counter-regulation mediated by IL-4.

Original languageEnglish (US)
Pages (from-to)206-214
Number of pages9
JournalNature Medicine
Volume7
Issue number2
DOIs
StatePublished - Feb 22 2001
Externally publishedYes

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T-cells
Antigen-Presenting Cells
Interleukin-4
Dendritic Cells
T-Lymphocytes
Antigens
Autoimmunity
Autoimmune Diseases
Chemical activation
Ligands

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. / King, Cecile; Mueller Hoenger, Regula; Malo Cleary, Mary; Murali-Krishna, Kaja; Ahmed, Rafi; King, Ernest; Sarvetnick, Nora E.

In: Nature Medicine, Vol. 7, No. 2, 22.02.2001, p. 206-214.

Research output: Contribution to journalArticle

King C, Mueller Hoenger R, Malo Cleary M, Murali-Krishna K, Ahmed R, King E et al. Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. Nature Medicine. 2001 Feb 22;7(2):206-214. https://doi.org/10.1038/84659
King, Cecile ; Mueller Hoenger, Regula ; Malo Cleary, Mary ; Murali-Krishna, Kaja ; Ahmed, Rafi ; King, Ernest ; Sarvetnick, Nora E. / Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. In: Nature Medicine. 2001 ; Vol. 7, No. 2. pp. 206-214.
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