T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice

Linda Myers, David L. Cullins, David Brand, Sandra Kleinau, John Stuart, Andrew Kang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective To explore the characteristics of the T cell population that responds to an analog peptide (A9) of type II collagen and regulates autoimmunity, using the collagen-induced arthritis (CIA) model. Methods Analog peptide A9 is a 26-amino acid peptide analogous to the sequence of a segment of type II collagen (CII245-270) but with substitutions at amino acid positions 260 (alanine for isoleucine), 261 (hydroxyproline for alanine), and 263 (asparagine for phenylalanine). We previously showed that A9 profoundly suppressed CIA and immune responses to type II collagen. In order to determine the mechanism of suppression, we used transgenic mice whose T cells express a type II collagen-specific receptor (T cell receptor) and performed passive cell transfer experiments. Results The results demonstrated that suppression of CIA by A9 is dependent on T cells. Using multiparameter flow cytometry, we determined that the cells responsible for suppression were CD4+ and expressed high levels of Fcε receptor Iγ chain (FcRγ). To establish the significance of this finding, we obtained mice genetically deficient in FcRγ in order to perform passive transfer experiments. The resulting FcRγ-/- CD4+ T cells, when primed by culture with A9, could not transfer the suppression of arthritis or secrete cytokines in response to A9. Conclusion Taken together, the results of this study suggest that the suppression of arthritis and the Th2 cytokine profile elicited by A9 is dependent on the presence of FcRγ in T cells. These findings are novel and may have therapeutic potential for patients with autoimmune arthritis.

Original languageEnglish (US)
Pages (from-to)2661-2670
Number of pages10
JournalArthritis and rheumatism
Volume63
Issue number9
DOIs
StatePublished - Sep 1 2011

Fingerprint

Collagen Type II
Fc Receptors
Interleukin-4
Arthritis
Experimental Arthritis
T-Lymphocytes
Peptides
Alanine
Collagen Receptors
Cytokines
Isoleucine
Asparagine
Hydroxyproline
Amino Acid Substitution
T-Cell Antigen Receptor
Phenylalanine
Autoimmunity
Transgenic Mice
Flow Cytometry
Amino Acids

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice. / Myers, Linda; Cullins, David L.; Brand, David; Kleinau, Sandra; Stuart, John; Kang, Andrew.

In: Arthritis and rheumatism, Vol. 63, No. 9, 01.09.2011, p. 2661-2670.

Research output: Contribution to journalArticle

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