Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondrocytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose. Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and expression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute. They did not express type X collagen or versican mRNA. These cells synthesized and secreted extracellular matrix molecules that were reactive with monoclonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4-and chondroitin-6-sulfate. Interleukin-1,8 (IL-1p) decreased the levels of type II collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1, c-fos, c-jun, and jun-B). These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1p8 suppressed this expression by 50-80%. These results show that immortalized human chondrocytes displaying cartilage-specific modulation by IL-1,3 can be used as a model for studying normal and pathological repair mechanisms. (J. Clin. Invest. 1994. 94:2307-2316

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Summary:would be expected for non-BMT patients. The patients reported here fall into two groups, an early onset group associated with cold autoantibodies and a late onset group We reviewed the medical records of 293 patients who underwent allogeneic bone marrow transplants at the associated with warm antibodies. In the early group the antibodies occurred between 2 to 8 months and in the late Hammersmith Hospital between 1989 and 1994. There was clinical evidence of an autoimmune reaction against onset group between 6 and 18 months post-transplant. We discuss the relationship between these phenomena and the red cells in nine patients. Seven of these patients had significant haemolysis; the other two had red cell autorole of factors such as GVHD, relapse, CMV and immunosuppression and also the association with the regenerating agglutination. Haemolysis was resistant to treatment in three cases. Six of the nine patients had monoclonal Ig immune system following BMT. bands identified within 1 year of transplant. The autoimmune reaction could be classified broadly into two types: an early onset type (n = 4) beginning 2 to 8Patients and methods months post-transplant associated with a cold antibody, and a late onset type (n = 5) beginning 6 to 18 months From the 293 patients who underwent allogeneic BMT at post-transplant associated with warm antibodies. The the Hammersmith Hospital, we identified nine patients with predominant antibody in the two categories described documented anti-red cell autoantibodies (red cell autoimmay reflect the kinetics of immune reconstitution postmunisation, RCAI). These patients were identified because transplant, since serum IgM levels typically return to they had clinically evident haemolysis (falling Hb with normal 2 to 6 months post-transplant, while IgG levels elevated bilirubin and reticulocytosis) or blood film abnormay not reach normal levels until 12-18 months postmality (eg agglutination). Patient and BMT details are transplant. We speculate that unbalanced reconstitution shown in Table 1. Two donor-recipient pairs had minor of B and T cell lymphopoiesis post-transplant may fav-ABO mismatch, one a major and one a bidirectional ABO our emergence of oligoclonal proliferation and that mismatch. All were matched for Rh D type. Haemolytic some of the resulting antibodies may have activity episodes attributable to ABO and Rh incompatibility are against red cells. not included in this report. One of the cases (No. 4) has

Summary:example, the way CsA is used either alone or in combination with MTX varies considerably from centre to centre. A survey was carried out among EBMT (EuropeanThere are differences in the route of administration, initial Group for Blood and Marrow Transplantation) centres dosage, policy of adjusting the dose during prophylaxis, of the practical details of the prophylaxis and treatment duration of prophylaxis, preparation used, etc. Acute of acute GVHD. The emphasis was on the prophylactic GVHD is usually treated with corticosteroids, but the use of cyclosporine A and methotrexate and their comdetails of treatment differ. The initial corticosteroid dose bination, and on the initial treatment of acute GVHD.is known to vary markedly, and the criteria for initiating Eighty-seven centres sent a report. This survey demontreatment are not uniform. Differences of this kind can be strated that marked differences exist between centres in expected to affect the results achieved with allogeneic SCT, the practices of GVHD prophylaxis and treatment and the lack of information of the actual protocols complidespite superficially similar protocols. These differences cates the interpretation and comparison of results from difmay have an impact on the results obtained. ferent trials.