Immune Regulation in Adjuvant Disease and Other Arthritis Models: Relevance to Pathogenesis of Chronic Arthritis

Abstract

Experimental models of arthritis and their human counterparts fall into three distinct classes: (a) responses of T cells to disseminated microbial antigens (Ags) as such; (b) responses of T cells to cartilage autoAgs; and (c) responses of T cells to major histocompatibility complex (HLA‐B27, DRB1) or other membrane components (LFA‐1) expressed on bone marrow‐derived cells. The primary immune response is driven, in naturally occurring disease, by microbial infection, e.g. with streptococci, enteric gram‐negative rods or spirochetes, or is experimentally induced with mycobacterial and other adjuvants. The response to cartilage components, such as collagen type‐II and various proteoglycans, may be driven by cross‐reactive microbial Ags, heat shock proteins (HSPs) in particular, or the adjuvant effect of intense primary joint inflammation, as in rheumatoid arthritis and the spondyloarthropathies. Adjuvant disease appears to be purely T‐cell‐mediated, whereas both T cells and antibody play a role in collagen and many other forms of arthritis. Experimental evidence suggests a pathogenetic role for T‐cell receptor γδ T cells in some lesions. Arthritis may be regulated by microbial and tissue HSPs, when these are administered by a nonimmunizing route or as altered peptide ligands, by anti‐idiotypic responses that block the action of effector T cells, and by competing Ags. Immune regulation involving natural killer (NK), NK T and certain subsets of γδ and αβ T cells, which may affect the occurrence, localization and character of this group of diseases, presents a challenge for further investigation.

The T Cells Specific for the Carboxyl-Terminal Determinants of Self (Rat) Heat-Shock Protein 65 Escape Tolerance Induction and Are Involved in Regulation of Autoimmune Arthritis

“…Lewis rats (RT.1 l ) challenged with heat-killed Mycobacterium tuberculosis H37Ra (Mtb) develop polyarthritis (adjuvant-induced arthritis; AA) that has several features resembling human RA (1,2). Studies in the AA model as well as analysis of peripheral blood-and synovial fluid-derived T cells of RA patients suggest that T cell responses to the 65-kDa mycobacterial heat-shock protein (Bhsp65) are involved in the pathogenesis of autoimmune arthritis (3)(4)(5)(6)(7)(8)(9). Bhsp65 contains both arthritogenic and disease-regulating T cell epitopes (4, 6, 10 -14).…”

Rheumatoid Arthritis: Laboratory Models of the Disease

“…Развитие тяжелого полиартрита наблюдается быстро -клинические признаки артрита возникают примерно через 10 дней по-сле инъекции адъюванта, реже -более чем через месяц [57]. Морфологические исследования сре-зов демонстрируют клеточную инфильтрацию, особенно нейтрофильную, и деструкцию сустава.…”

“…При формировании AIA наблюдается значительная выраженность та-кого признака РА, как резорбция кости; разруше-ние хрящевой ткани встречается реже, чем при РА человека [2]. В отличие от РА, позвоночник, гастроинтестинальный и мочеполовой тракты, кожа и глаза также поражаются [57], что отмеча-ется при спондилоартропатиях у человека. В па-тогенез AIA вовлечены T-клетки и нейтрофилы; считается, что модель является комплемент-не-зависимой.…”

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

“…Because AIA is undiminished in rats thymectomized at birth and given adjuvant as adults (18), it was inferred that TCR␥/␦ T cells mediated disease in the absence of ␣/␤ T cells (19). An important subset of ␥/␦ T cells leave the rat thymus well before birth, are unaffected by neonatal thymectomy (20), and have been shown to function as polarized Th1 effectors in a variety of experimental and natural situations (see ref.…”

“…An important subset of ␥/␦ T cells leave the rat thymus well before birth, are unaffected by neonatal thymectomy (20), and have been shown to function as polarized Th1 effectors in a variety of experimental and natural situations (see ref. 19). In contrast, depletion of ␥/␦ T cells from birth did not prevent or ameliorate AIA (21).…”