Failure of autologous mixed lymphocyte reactions between T and non-T cells in patients with systemic lupus erythematosus.

Abstract

Normal human T cells proliferate vigorously when stimulated with autologous non-T cells. This autologous mixed lymphocyte reaction (MLR) between T and non-T cells was defective in patients with active systemic lupus erythematosus (SLE) In contrast, T cells and non-T cells from active SLE patients behaved normally as responding and stimulating cells, respectively, in the allogeneic MLR. Systemic lupus erythematosus (SLE) is a complex multisystem autoimmune disease. One of its most prominent features is the presence of a wide variety of autoantibodies in the serum. In addition, several T cell defects have been described in patients with active SLE. It has been postulated that the excessive production of autoantibodies is due to some abnormality in B cell regulation by T cells (1, 2). More specifically, evidence has been presented to suggest a relative lack of suppressor T cell function in such patients (3-5).In the course of our studies of suppressor T cell function in patients with SLE (5), we made the unexpected observation that, when lymphocytes from patients with SLE were used, the autologous mixed lymphocyte reaction (MLR) failed to occur.That is, whereas T cells from normal individuals proliferate vigorously in response to autologous non-T cells, T cells from SLE patients failed to proliferate normally in response to autologous non-T cells. In these studies we have investigated the reason for this defect in patients with SLE.Because it has been recently proposed that "autologous MLR reflect a mechanism by which T lymphocytes regulate lymphocyte function" (6), the absence of such a reaction in the lymphocytes of patients with SLE is particularly provoca-

Immunoregulatory T cell function in patients with primary biliary cirrhosis.

“…Thus, the decreased Con A-induced suppressor activity in patients with PBC may represent a close relation to the reduction of AMLR. The same defect of both Con A-induced suppressor activity and AMLR has been reported in patients with systemic lupus erythematosus (Sakane and Steinberg 1978) and with chronic active hepatitis (Nonomura et al 1982). Our present data suggest that serum factor(s) inhibitory to lymphocyte transformation responses by Con A and PHA are present in a majority of patients with PBC.…”

“…Derangement of suppressor T cell function has been reported in various human diseases such as hypogammaglobulinemia (Siegal et al 1976), Hodgkin's disease (Twomey et al 1975), systemic lupus erythematosus (Sagawa and Abdou 1979), ulcerative colitis and Crohn's disease (Hodgson et al 1978a), juvenile rheumatoid arthritis (Strelkauskas et al 1978), chronic active hepatitis (Hodgson et al 1978b; Nonomura et al 1982) and insulin-dependent diabetes mellitus (Buschard et al 1980). Recently, autologous mixed lymphocyte reaction (AMLR), in which human T cells respond to mitomycin-C treated or X-irradiated autologous non-T cells, is employed to investigate immunoregulatory functoins (Sakane and Steinberg 1978). AMLR was found to be decreased in patients with systemic lupus erythematosus (Sakane and Steinberg 1978), Sjogren's syndrome (Miyasaka et al 1980) and chronic activie hepatitis (Nonomura et al 1982 …”

Studies of immune functions of patients with systemic lupus erythematosus

“…Recently, we have found that the autologous mixed lymphocyte reaction is markedly diminished in patients with active SLE and decreased in some patients with inactive SLE (4 …”

CD8+/DR+ T gamma cells inhibit the autologous mixed lymphocyte reaction

“…1977;Engleman et al, 1982). Early investigations demonstrated abnormal AMLR in patients with lymphoproliferative and autoimmune diseases (Sakane, Steinberg & Green, 1978;Miyasaka et al, 1980;Engleman et al, 1980), and consequently this assay has gained increasing use in the clinical assessment of immunity. Also, because both effector (cytotoxicity and antibody production) and regulatory (help and suppression) functions are generated during in vitro culture, the AMLR has been used to study interactions between mononuelear eell subsets (Tomanari, 1980;Gatenby, Kotzin & Engleman, 1981;Kotani et al, 1984).…”