The Expression of Major Histocompatibility Antigens on Human Articular Chondrocytes

Lance, Eugene M.; Kimura, Lucille H.; Manibog, Carolyn N.

doi:10.1097/00003086-199306000-00032

Cited by 33 publications

(24 citation statements)

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“…Moreover, the expression of these HLAs (HLA class II) have been detected in chondrocytes of RA patients (28,29). From our study, we hypothesize that the expression of MHC class II on target organs can increase their sensitivity to arthritogenic stimuli in general.…”

Section: Discussionmentioning

confidence: 58%

Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Kanazawa¹,

Ota²,

Sekine

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain MHC class II molecules. To clarify the role of these determinants in RA, we generated the D1CC transgenic mouse that expressed genes involved in antigen processing and presentation by the MHC class II pathway in joints. The class II transactivator, which was transcribed from the rat collagen type II promoter and enhancer, directed the expression of these genes. In D1CC mice congenic for the H-2 q (DBA͞1) background, small amounts of bovine collagen type II in adjuvant induced reproducibly an inflammatory arthritis resembling RA. Importantly, these stimuli had no effect in DBA͞1 mice. Eighty-nine percent of D1CC mice developed chronic disease with joint swelling, redness, and heat in association with synovial proliferation as well as pannus formation and mononuclear infiltration of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and interstitial pneumonitis also were observed. As in patients with RA, anticyclic citrullinated peptide antibodies were detected during the inflammatory stage. Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe joint space narrowing, and erosions, which led to ankylosis, but without the appearance of osteophytes. Thus, aberrant expression of MHC class II in joints facilitates the development of severe erosive inflammatory polyarthritis, which is very similar to RA. autoimmunity ͉ class II transactivator ͉ transgenic mouse ͉ nodules ͉ pneumonitis R heumatoid arthritis (RA) is a chronic inflammatory disease with symmetrical inflammatory and erosive polyarthritis of synovial joints and a variety of extraarticular manifestations. Particular MHC class II alleles such as DRB0401, DRB0404, and DQ8 are linked to RA in 30-50% of cases (1-3). To examine possible mechanisms of RA, many models of inflammatory arthritis have been developed in the mouse and rat (4, 5). Among these models, collagen-induced arthritis (CIA) leads to acute inflammation, osteophytosis, and destruction of bone in DBA͞1 and B10.Q (H2 q ) strains of mice (6, 7). In these mice, passively transferred autoantibodies against CII, or the injection of a combination of certain monoclonal anti-CII antibodies, also induce rapid inflammation of joints (8,9). A recently discovered model, the SKG mouse, contains mutations in the chainassociated protein of 70 kDa (ZAP-70) that is involved in the signaling from the T cell antigen receptor (10). In these mice, infection with fungi or immunization with zymosan can induce a chronic inflammatory arthritis (11). In K͞BxN mice, chronic arthritis develops spontaneously because anti-G6PI antibodies accumulate in serum and joints, leading to inflammatory arthritis and bone destruction (12,13). In all these mice and several other models, the onset and progression of inflammatory arthritis have been well characterized and analyzed. However, how faithfully these small animal models resemble RA and what roles MHC class II play in their disease have remained elusive.MHC cla...

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Section: Discussionmentioning

confidence: 58%

Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Kanazawa¹,

Ota²,

Sekine

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Of the biologic and synthetic vehicles, autogenous fibrin provides an arthroscopically applicable stable fixation and some immune protection for the transplanted chondrocytes (26,27,47). However, the use of allograft chondrocytes carries some residual risk of an immune reaction to the transplanted cells (28,37,39,71). Autogenous chondrocytes eliminate this risk, although the articular morbidity of the donor site and the cost and risk of a second general anesthesia make autogenous cartilage harvest undesirable (48).…”

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confidence: 99%

Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites

Nixon

Fortier

Williams

et al. 1999

Journal Orthopaedic Research

197

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Summary: Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin-like growth factor-1 facilitates chondrogenesis of bone marrow-derived stem cells in long-term culture and may enhance chondrogenesis in healing cartilage lesions in vivo. This study examined the impact of insulin-like growth factor-I, gradually released from fibrin clots polymerized in situ, on the recruitable stem-cell pool in a full-thickness critical cartilage defect model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 kg of human recombinant insulin-like growth factor-I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and I1 collagen immunohistochemistry, types T and IT collagen in situ hybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-11 procollagen mKNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type-I1 collagen showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-IT message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and remote cartilage of the treated and control joints. The proportion of type-I1 collagen significantly increascd in growth factor-treated tissues. Fibrin polymers laden with insulin-like growth factor-I improved the histologic appearance and thc proportion of type-I1 collagen in healing, full-thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.Traumatic articular cartilage injuries in adults are common; however, the intrinsic repair is generally minimal, and the healed tissue has many characteristics of fibrous tissue rather than of hyaline cartilage (9,21). Biomechanical shear at the interface of repair and residual cartilage also disrupts the new tissue, leading to the reappearance of pain, synovial reaction, and chronic dysfunction. Numerous techniques have been used experimentally or clinically in an attempt to improve the integrity of the repair ti...

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“…In support of this claim, other researchers have discovered that MHC II is present in isolated chondrocytes and absent in intact, healthy cartilage. 26,[46][47][48] Immunostaining for MHC II in native bovine and leporine articular cartilage used in this study also showed that these markers were not present in situ. Overall, the results of this study are in accord with those of previous studies demonstrating the presence of MHC II on chondrocytes isolated from healthy cartilage.…”

Section: Discussionmentioning

confidence: 91%

“…26,43,44 In particular, chondrocytes isolated from arthritic joints have been shown to possess higher amounts of MHC II molecules and are more immune-reactive when used in an MLR assay than chondrocytes from healthy joints. [43][44][45][46] Although the cells used in this study were not isolated from arthritic joints, it is possible that the insult due to enzymatic digestion of the cartilage matrix induced the cells to transition to a phenotype more amenable to antigen presentation. In support of this claim, other researchers have discovered that MHC II is present in isolated chondrocytes and absent in intact, healthy cartilage.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of Bovine and Leporine Articular Chondrocytes and Meniscus Cells

Huey

Willard

Athanasiou

2012

Tissue Engineering Part A

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Immune rejection is a major concern for any allogeneic or xenogeneic graft. For in vivo investigations of cartilage tissue engineering strategies, small animal models such as the leporine model are commonly employed. Many studies report little to no immune rejection upon allogeneic or xenogeneic implantation of native articular and meniscal cartilages. This study investigated whether bovine and leporine articular chondrocytes (ACs) and meniscus cells (MCs) have immunoprivileged characteristics because of their ability to stimulate proliferation of leporine peripheral blood mononuclear cells (PBMCs) in vitro. After 6 days of co-culture, none of the cell types caused a proliferative response in the leporine PBMCs, indicating that these cells may not elicit immune rejection in vivo. Reverse transcriptase polymerase chain reaction analysis for major histocompatibility complex class (MHC) I and II and costimulation factors CD80 and CD86 revealed that all cell types produced messenger RNA for MHC I and II, but only some were CD80 or CD86 positive, and none were positive for both costimulation factors. Flow cytometry found that bovine MCs and ACs displayed MHC II (MCs: 32.5%, ACs: 14.4%), whereas only leporine ACs were MHC II positive (7.5%). Although present in isolated cells, MHC I and II were not observed in intact bovine or leporine hyaline cartilage or meniscus tissues. Despite some presence of MHC II and costimulation factors, none of the cell types studied were able to cause PBMC proliferation. These findings indicate that bovine and leporine MCs and ACs share a similar immunoprivileged profile, bolstering their use as allogeneic and xenogeneic cell sources for engineered cartilage.

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The Expression of Major Histocompatibility Antigens on Human Articular Chondrocytes

Cited by 33 publications

References 0 publications

Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites

Immunogenicity of Bovine and Leporine Articular Chondrocytes and Meniscus Cells

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