concanavalin-a and Diseases-in-Twins

Immunoregulatory defects have been suggested in autoimmune disorders including Graves' disease. The finding that Concanavalin A-induced suppressor T cell function was sub-optimal in Graves' disease has been disputed; a restricted defect in TSH-receptor antigen-specific suppressor cells has instead been proposed by Okita et al. (1980). To explore this further, we studied both specific and non-specific suppressor cell function in a pair of HLA identical twins, one of whom had Graves' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/10(6) cells) the patient's mononuclear cells (MNCs) incorporated more (3H)-thymidine (7365 cpm/10(6) cells) in response to thyroid membrane antigen (TMA). Removal of glass-adherent cells before addition of antigen increased (3H)-uptake by cells from the healthy twin to 1808 cpm but reduced those from the Graves' twin to 3411 cpm. The influence of MNCs cultured with Con A or TMA for 24 h upon (3H)-thymidine uptake by 2 X 10(6) indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non-specific and specific suppressor cell function respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H-thymidine uptake 3250 vs 7365 cpm/10(6). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/10(6) cells). We conclude that (1) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) the increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of (3H) incorporation upon their removal; (3) in the patient, the specific suppressor cell defect is more severe than the non-specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory defect in Graves' disease.

Topics: Adult; Antigens, Surface; Cell Division; Concanavalin A; Diseases in Twins; Female; Graves Disease; Humans; Lymphocyte Activation; Pregnancy; T-Lymphocytes, Regulatory; Thymidine; Thyroid Gland; Twins, Monozygotic

Immunological reactivity in patients with SLE was studied in vitro trinitrobenzene sulphonate (TNP) specific antibody formation by peripheral blood lymphocytes. Lymphocytes from patients with SLE could produce an increased number of TNP-specific plaque-forming cells (PFC), while no such response could be seen in normal controls. Co-culture of lymphocytes from active SLE patients and normal controls was performed with TNP-Horse red blood cells (TNP-HRBC). The number of PFC by B lymphocytes from active SLE patients was suppressed by T lymphocytes from normal controls. On the other hand, the number of PFC by B lymphocytes from normal controls was increased by T lymphocytes from active SLE patients. Co-culture of lymphocytes from identical twins discordant for SLE was also performed, and the same results were obtained. We further examined the effects of Con A on antibody formation. Con A-treated T lymphocytes from a normal control markedly suppressed TNP-specific PFC by peripheral lymphocytes from active SLE patients. However, Con A-treated T lymphocytes from an active SLE patient did not suppress TNP-specific PFC by lymphocytes from another active SLE patient. These results suggest that active SLE patients showed a loss of suppressor T-lymphocyte function.

Topics: Adolescent; Adult; Antibody Formation; Concanavalin A; Diseases in Twins; Female; Hemolytic Plaque Technique; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Male; Middle Aged; Rosette Formation; T-Lymphocytes

We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.

Topics: Aged; Concanavalin A; Diseases in Twins; DNA; Female; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitogens; Pregnancy; Skin Tests; Twins, Dizygotic; Twins, Monozygotic