Joseph Holoshitz

Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II.

We have been studying the pathogenesis of adjuvant arthritis in rats using a long-term cell line of T lymphocytes, the A2 line, which can induce polyarthritis and can also be used to vaccinate rats against adjuvant arthritis. Although line A2 was selected for its proliferative response to mycobacteria, it also responded to collagen type II. To elucidate its role of responsiveness to collagen type II and the relationship between arthritogenicity and vaccination, we cloned A2 and selected a subline A2b. We now report that subline A2b, which bore a marker of helper/delayed hypersensitivity T lymphocytes, was strongly arthritogenic, but could not vaccinate against arthritis. Moreover, A2b showed no response to collagen type II. Therefore, reactivity to collagen type II is not a requisite for arthritogenicity, and mediation of arthritis and vaccination can be distinct properties of different populations of T lymphocytes.

T LYMPHOCYTES OF RHEUMATOID ARTHRITIS PATIENTS SHOW AUGMENTED REACTIVITY TO A FRACTION OF MYCOBACTERIA CROSS-REACTIVE WITH CARTILAGE

An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA.

Vaccination against autoimmune disease with lines of autoimmune T lymphocytes

The etiological agents of auto mmune diseases are endogenous lymphocytes which attack apparently normal constituents of the individual, while in infectious disease the individual is attacked by an exogenous microbial agent. Nevertheless, the clinical expression of autoimmunity and infection may result from similar pathological processes of edema, cellular infiltration, phagocytosis, cytotoxicity, fibrosis, calcification, etc. And as Irun Cohen and colleagues show here both types of illness can be studied to advantage by the basic strategy of isolating in pure culture the etiological agent of disease.

Role of the thymus in induction and transfer of vaccination against adjuvant arthritis with a T lymphocyte line in rats.

Adjuvant arthritis is an experimental disease of rats induced by immunization to antigens of Mycobacterium tuberculosis. Our observation that arthritis could be induced in irradiated rats by the A2 line of T lymphocytes in the absence of mycobacterial antigens suggested that adjuvant arthritis is an autoimmune disease. Moreover, the A2 line could be used to vaccinate unirradiated rats against the subsequent induction of adjuvant arthritis by active immunization to Mycobacteria. In the present study we found that thymus cells obtained from A2 vaccinated rats could transfer resistance to adjuvant arthritis to naive rats. This indicates that the mechanism of resistance induced by A2 vaccination is probably immunological and involves thymus-derived lymphocytes.

Listeria Monocytogenes Pericarditis in a Chronically Hemodialyzed Patient

We describe the third documented case of Listeria monocytogenes pericarditis. This occurred in a 54-year-old woman with end-stage renal failure on chronic hemodialysis. Her initial presentation was one of Listeria monocytogenes bacteremia, which apparently responded to two weeks of cefazolin sodium therapy. After cessation of therapy the patient returned with Listeria monocytogenes pericarditis, this responding completely to four weeks of erythromycin therapy. We could not rule out coexisting endocarditis, especially since we found high levels of circulating immune complexes which subsided as the patients condition improved. Further immunological studies displayed a decrease in cellular functions. This case illustrates the importance of Listeria monocytogenes as a human pathogen in immunocompromised patients. Listeria should be included among the potential causative agents of pericarditis in such patients.