Intravenous tolerization with type II collagen induces interleukin-4- and interleukin-10-producing CD4+ T cells

M. L. Gumanovskaya, Linda Myers, E. F. Rosloniec, John Stuart, Andrew Kang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Intravenous (i.v.) administration of type II collagen (CII) is an effective way to induce tolerance and suppress disease in the collagen- induced arthritis (CIA) model. In this study, we demonstrated that a single i.v. dose of CII (as low as 0.1 mg/mouse) completely prevented the development of CIA. This suppression was accompanied by decreases in levels of antibody specific for the immunogen, bovine CII and autoantigen, mouse CII. Splenocytes obtained from CII-tolerized mice and stimulated with CII in vitro produced predominantly the T helper 2 (Th2)-type cytokines interleukin- 4 (IL-4) and interleukin-10 (IL-10). In contrast, cells obtained from mice immunized with CII produced predominantly interferon-γ (IFN-γ). Two-colour flow cytometric analysis of cytokine expression and T-cell phenotype demonstrated that CD4+ cells and not CD8+ or γδ+ cells were the predominant regulatory cells producing IL-4 and IL-10. Transgenic mice bearing a T-cell receptor (TCR) specific for CII had a greater increase in the number of IL-4-secreting CD4+ cells, as well as a marked increase of IL- 4 in culture supernatants. This cytokine was produced by transgene-bearing T cells. Elucidation of mechanisms for the induction of tolerance in mature T cells is an important line of study in autoimmune models because of the potential application for treating organ-specific autoimmune disease.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalImmunology
Volume97
Issue number3
DOIs
StatePublished - Jul 17 1999

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Collagen Type II
Interleukin-4
Interleukin-10
T-Lymphocytes
Experimental Arthritis
Cytokines
Autoantigens
T-Cell Antigen Receptor
Transgenes
Intravenous Administration
Interferons
Transgenic Mice
Autoimmune Diseases
Color
Phenotype
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Intravenous tolerization with type II collagen induces interleukin-4- and interleukin-10-producing CD4+ T cells. / Gumanovskaya, M. L.; Myers, Linda; Rosloniec, E. F.; Stuart, John; Kang, Andrew.

In: Immunology, Vol. 97, No. 3, 17.07.1999, p. 466-473.

Research output: Contribution to journalArticle

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