Hunt D W, Corson L, Barker H D, Levy J G, Petty R E
Department of Paediatrics, University of British Columbia, Vancouver, Canada.
J Autoimmun. 1993 Dec;6(6):691-700. doi: 10.1006/jaut.1993.1058.
Adjuvant arthritis (AA) and type II collagen (CII)-induced arthritis (CIA) in the rat serve as models of chronic human arthritis. Adoptive transfer of AA was observed in 21 of 25 Lewis rats given concanavalin A (Con A)-treated spleen cells prepared from animals immunized with Mycobacterium butyricum in mineral oil (complete Freund's adjuvant, CFA). No arthritic changes were noted in rats given spleen cells obtained from donors that had received incomplete Freund's adjuvant (IFA, 0/22), type I collagen in IFA (CI-IFA, 0/6) or CII-IFA (0/28). Administration of spleen cells from IFA, CI-IFA or CII-IFA-injected animals did not modify the development of CIA when these rats were subsequently challenged with CII-IFA. However, partial protection against induction of AA was provided by the transfer of spleen cells prepared from rats immunized with CII-IFA (6/11) but not by those obtained from rats injected with IFA (1/15) or CI-IFA (0/3). Rats that did not develop clinically evident arthritis following the administration of spleen cells prepared from CFA-injected rats were also resistant to AA induction by CFA. Pre-treatment of rats with a synthetic peptide, corresponding to amino acids 180-188 of the Mycobacterium 65 kD heat shock protein (65 kD HSP), significantly delayed the onset of AA, but not that of CIA. Disease-specific resistance to AA, provided by spleen cells prepared from rats injected with CII-IFA and by pre-treatment with the 65 kD HSP 180-188 peptide, may result from the induction of protective tolerance to arthritogenic epitopes present in the Mycobacterium and CII preparations.
大鼠佐剂性关节炎（AA）和Ⅱ型胶原（CII）诱导的关节炎（CIA）可作为人类慢性关节炎的模型。在25只Lewis大鼠中，有21只接受了用刀豆蛋白A（Con A）处理的脾细胞，这些脾细胞取自于在矿物油（完全弗氏佐剂，CFA）中用丁酸分枝杆菌免疫的动物，观察到了AA的过继转移。给大鼠注射从接受不完全弗氏佐剂（IFA，0/22）、IFA中的Ⅰ型胶原（CI-IFA，0/6）或CII-IFA（0/28）的供体获得的脾细胞后，未观察到关节炎变化。当这些大鼠随后用CII-IFA攻击时，注射IFA、CI-IFA或CII-IFA动物的脾细胞给药并未改变CIA的发展。然而，用CII-IFA免疫的大鼠制备的脾细胞转移提供了对AA诱导的部分保护（6/11），而注射IFA（1/15）或CI-IFA（0/3）的大鼠制备的脾细胞则没有提供这种保护。在用CFA注射大鼠制备的脾细胞给药后未出现临床明显关节炎的大鼠，对CFA诱导的AA也具有抗性。用与分枝杆菌65 kD热休克蛋白（65 kD HSP）的180-188位氨基酸对应的合成肽预处理大鼠，可显著延迟AA的发病，但不延迟CIA的发病。由注射CII-IFA的大鼠制备的脾细胞以及用65 kD HSP 180-188肽预处理所提供的针对AA的疾病特异性抗性，可能是由于对分枝杆菌和CII制剂中存在的致关节炎表位诱导了保护性耐受所致。
