Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model. |
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Authors: | David D Brand Linda K Myers Karen B Whittington Kary A Latham John M Stuart Andrew H Kang Edward F Rosloniec |
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Institution: | Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA. dbrand@utmem.edu |
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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 Tg mice express an I-A(q)-restricted CII (260-267)-specific TCR that confers severe accelerated autoimmune arthritis following immunization with CII. Despite the fact that >90% of the alphabeta T cells express the Tg, these mice can be rendered completely tolerant to the induction of arthritis by i.v. administration of 200 microg 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 CD62L(low) and of phagocytic glycoprotein-1 to CD44(high), 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. |
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