Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells.
Antibodies against type II collagen (anti-CII) are arthritogenic and have a crucial role in the initiation of collagen-induced arthritis. Here, we have determined the dependence of T and B cells in collagen-antibody-induced arthritis (CAIA) during different phases of arthritis. Mice deficient for B and/or T cells were susceptible to the CAIA, showing that the antibodies induce arthritis even in the absence of an adaptive immune system. To determine whether CII-reactive T cells could have a role in enhancing arthritis development at the effector level of arthritis pathogenesis, we established a T cell line reactive with CII. This T cell line was oligoclonal and responded to different post-translational forms of the major CII epitope at position 260-270 bound to the Aq class II molecule. Importantly, it cross-reacted with the mouse peptide although it is bound with lower affinity to the Aq molecule than the corresponding rat peptide. The T cell line could not induce clinical arthritis per se in Aq-expressing mice even if these mice expressed the major heterologous CII epitope in cartilage, as in the transgenic MMC (mutated mouse collagen) mouse. However, a combined treatment with anti-CII monoclonal antibodies and CII-reactive T cells enhanced the progression of severe arthritis.
Nandakumar
Kutty Selva
KS
Section for Medical Inflammation Research, Lund University, Sweden. nan@inflam.lu.se
Bäcklund
Johan
J
Vestberg
Mikael
M
Holmdahl
Rikard
R
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000633:toxicity*; D000918:Antibody Specificity; D001169:Arthritis, Experimental / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D024043:Collagen Type II / Q000737:chemistry / Q000276:immunology*; D003433:Crosses, Genetic; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta