Virus resistance transferred from human rheumatoid cells to rabbit synovial cells. I. Methods and results of intra-articular injection of human cells into rabbit joints.
Authors: C Smith, D Hamerman, R Janis, E Habermann
Journal: Annals of the Rheumatic Diseases (1974)

In histological sections of the synovial membrane obtained from patients with rheumatoid arthritis, the lining cells display a number of alterations that distinguish them from the lining cells of the normal synovial membrane.The rheumatoid lining cells synthesize decreased amounts of a component immunologically related to cartilage protein polysaccharide, and demonstrate altered and enhanced lysosomal hydrolase activities (Hamerman, Barland, and Janis, 1969), which may account for the finding of an excess of reduced form of nicotinamide adenine dinucleotide phosphate in these cells (Chayen and Bitensky, 1971).Synovial cells originating from rheu- matoid membranes after explant culture continue to manifest these differences in vitro (Smith and Hamerman, 1969).They also display increased glucose consumption and lactate production, and enhanced synthesis of hyaluronate (Castor, 1971).Rheumatoid synovial cells (RSC) in culture are also resistant to productive infection by Newcastle disease virus (NDV) (Smith and Hamerman, 1969) and rubella virus (RV) (Grayzel and Beck, 1970).In our hands, this resistance to exogenous virus infection is a unique property of the cultured RSC, providing an apparently specific 'rheumatoid trait'.Synovial cells derived from nonrheumatoid joints (NSC) including normal, psoriatic, and tuberculous arthritis, have proven susceptible to lytic infection with RV in 67 of seventy experiments.Over fifty RSC cultures have been tested and all but three have been resistant to cytolytic RV infection.The basis for this resistance is not known, but does not appear to be due to enhanced production of interferon by rheumatoid cells; indeed these cells seem less respon- sive than normal cells to interferon inducers (Grayzel and Beck, 1970).An infectious agent has long been sought as the aetiologic basis for rheumatoid arthritis, but until recently there was little evidence for such a possibility.Reports have now appeared describing the isolation of diphtheroid organisms from rheumatoid joints (Stewart, Alexander, and Duthie, 1969; Bartholomew and Nelson, 1972), as well as a number of types of fastidious mycoplasma (Jansson, Makisara, Vainio, Vainio, Snellman, and Tuuri, 1971; Williams, Brostoff, and Roitt, 1970; Fraser, Shirodaria, Haire, and Middleton, 1971).However, recent studies fail to confirm the association of mycoplasma with rheu- matoid joint tissues (Ward, Cole, and Smith, 1972).Despite numerous attempts using conventional techniques, no virus agent has been isolated from rheumatoid synovial membrane or synovial fluid (Smith and Hamerman, 1969).The possibility exists, however, that a latent virus persists in the RSC causing their resistance to exogenous virus infection and their altered metabolic reactions.This agent may be aetiologically related to rheumatoid arthritis.In recent years new virus-host cell interactions have been demonstrated, whereby non-lytic virus infections result in persistence of the virus genome in cells producing either cell transformation (oncogenic viruses) or slowly evolving cell dysfunction (slow