Reactivity patterns of synovial T-cell lines derived from a patient with rheumatoid arthritis. I. Reactions with defined antigens and auto-antigens suggest the existence of multireactive T-cell clones.

The functional T-cell repertoire in the inflamed joint of a patient with rheumatoid arthritis was analysed at the clonal level. Using limiting dilution techniques and selecting for growth of in vivo activated and/or autoreactive T cells, 149 T-cell lines were established. They were tested in a proliferation assay for reactivity against an autologous Epstein-Barr virus (EBV)-transformed B-cell line and a panel of auto-antigens and foreign antigens. Seventy-five lines (approximately 50%) could be stimulated. Thirty-six lines (approximately 24%) were antigen-reactive. They were stimulated by human collagens type I (15), II (10), IV (7) or V (4), cartilage proteoglycans (4), Mycobacterium tuberculosis (15), the 60 kDa heat-shock protein of M. bovis (13) or tetanus toxoid (10). T-cell lines were either monoreactive (19), bireactive (6), or multireactive (11), i.e. they were stimulated by either one, by two, or by more antigens in the panel. About half of the antigen-reactive lines were at the same time autoreactive towards the autologous B-cell line. These data suggest the existence of multispecific autoreactive T-cell receptors comparable to multireactive or natural autoantibodies and prove the presence of autoantigen-reactive T cells in the inflamed joints of patients with rheumatoid arthritis.

Evidence that functional deletion of donor-reactive T lymphocytes in kidney allograft recipients can occur at the level of cytotoxic T cells, IL-2-producing T cells, or both. A limiting dilution study.

The frequencies of circulating donor-reactive cytotoxic lymphocyte precursors (CLP) and Il-2-producing helper lymphocyte precursors (HLP) were determined by limiting dilution analysis in 19 kidney allograft recipients before and at various intervals (up to 2 years) after transplantation. A significant, selective, and stable reduction of the frequencies of donor-reactive (but not of third party-reactive) CLP and/or HLP was observed in some patients beginning 3 to 6 months after transplantation. One patient developed reduced frequency of CLP only, 3 patients reduced frequencies of HLP only, and 2 patients reduced frequencies of both CLP and HLP. The selective reduction of donor-reactive CLP and/or HLP frequencies ranged from 5-25-fold when compared with the pretransplantation level and was associated with stable graft function. These data indicate that functional deletion of circulating donor-reactive T cells can occur at the level of cytotoxic T lymphocytes, Il-2-producing helper T lymphocytes, or both. Implications of these findings for the individualization of immunosuppressive regimens will be discussed.