Systemic characteristics of chronic arthritis induced by transfer of humanrheumatoid synovial membrane into SCID mice (human/murine SCID arthritis)

Erosive human/murine (hu/mu) SCID arthritis, caused by unilateral engraftin g of human rheumatoid arthritis synovial membrane (RA-SM) in:the knee joint s of SCID mice, was monitored for up to 18 weeks by scintigraphic, radiolog ical, morphological and immunohistochemical analyses. Tc-99m-DPD scintigrap hy and histology revealed secondary, oligoarticular spreading of arthritis to contralateral knees and hips, but not to forelimb joints. Also, there we re no extraarticular manifestations. At 18 weeks, surviving human cells wer e found within the pannus, but not directly at the cartilage erosion front, where fibroblast-like cells and macrophages of murine origin predominated. The latter cells also predominated in secondarily affected joints, where n o human cells were detectable. preventive depletion of murine NK-cells by a nti-asialo-GMI antibodies, to check the-influence of NK cells-independently of strain and MHC system, combined with application of autologous human PB MN cells, had virtually no effects on the disease process. The completeness of the SCID defect was not critical, i.e. T cells were completely absent i n the organs examined, and the presence of a few B cells in the spleen did not correspond to particular disease features. The SCID defect itself had a clear impact, since, in the chronic phase, SCID.bg and RAG-2(-/-) knockout mice developed less consistent pathological/scintigraphic signs of disease -than SCID mice. Thus, unilaterally-induced hu/mu SCID arthritis is an olig oarticular disorder of the hindlimbs. Murine macrophages and fibroblast-lik e cells appear responsible for tissue destruction in engrafted and non-engr afted arthritic joints. (C) 1999 Academic Press.