Detection of Early Changes in Autoimmune T Cell Phenotype and Function Following Intravenous Administration of Type II Collagen in a TCR-Transgenic Model

• Published in: The Journal of immunology (1950) 2002-01, Vol.168 (1), p.490-498
• Main Authors: Brand, David D, Myers, Linda K, Whittington, Karen B, Latham, Kary A, Stuart, John M, Kang, Andrew H, Rosloniec, Edward F
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - metabolism; Arthritis, Experimental - chemically induced; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Autoimmune Diseases - chemically induced; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity; Cells, Cultured; Collagen Type II - administration & dosage; Collagen Type II - immunology; Cytokines - biosynthesis; Genes, T-Cell Receptor; Immunophenotyping; Injections, Intravenous; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Self Tolerance; T-Lymphocyte Subsets - classification; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.1.490

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.