Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model.
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.
Brand
David D
DD
Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA. dbrand@utmem.edu
Myers
Linda K
LK
Whittington
Karen B
KB
Latham
Kary A
KA
Stuart
John M
JM
Kang
Andrew H
AH
Rosloniec
Edward F
EF
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D002478:Cells, Cultured; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D019672:Genes, T-Cell Receptor; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets / Q000145:classification; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D024043:Collagen Type II; D016207:Cytokines