Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model

David Brand, Linda Myers, K. B. Whittington, K. A. Latham, John Stuart, Andrew Kang, E. F. Rosloniec

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31 Citations (Scopus)

Abstract

To study the phenotypic and functional changes in naive type II collagen (CII)-specific autoimmune T cells following a tolerogenic signal, a TCR-transgenic (Tg) mouse model of collagen-induced arthritis was developed. These 3Tg mice express an I-Aq-restricted CII (260-267)-specific TCR that confers severe accelerated autoimmune arthritis following immunization with CII. Despite the fact that >90% of the αβ T cells express the Tg, these mice can be rendered completely tolerant to the induction of arthritis by i.v. administration of 200 μg of CII. As early as 24 h after CII administration, CII-specific T cells demonstrated a decreased ability to proliferate in response to the CII immunodominant peptide and phenotypically altered the expression of L-selectin to CD62Llow and of phagocytic glycoprotein-1 to CD44high, expression levels consistent with the phenotype of memory T cells. In addition, they up-regulated the expression of the activation markers CD71 and CD69. Functionally, following tolerogenic stimulation, the CII-specific T cells produced similar levels of IL-2 in comparison to controls when challenged with CII peptide, however, by 48 h after exposure to tolerogen, IL-2 production dropped and was replaced by high levels of IL-10 and IL-4. Based on their production of Th2 cytokines, these data suggest that T regulatory cells expressing activation and memory markers are induced by the tolerogen and may exert their influence via cytokines to protect the animals from the induction of arthritis.

Original languageEnglish (US)
Pages (from-to)490-498
Number of pages9
JournalJournal of Immunology
Volume168
Issue number1
DOIs
StatePublished - Jan 1 2002

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Collagen Type II
Intravenous Administration
T-Lymphocytes
Phenotype
Arthritis
Transgenic Mice
Interleukin-2
Cytokines
L-Selectin
Peptides
Aptitude
Experimental Arthritis
Regulatory T-Lymphocytes
Interleukin-4
Interleukin-10
Immunization
Glycoproteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model. / Brand, David; Myers, Linda; Whittington, K. B.; Latham, K. A.; Stuart, John; Kang, Andrew; Rosloniec, E. F.

In: Journal of Immunology, Vol. 168, No. 1, 01.01.2002, p. 490-498.

Research output: Contribution to journalArticle

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