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STUDIES OF IMMUNOGLOBULIN SYNTHESIS IN CULTURES OF PERIPHERAL T AND B LYMPHOCYTES: REDUCED T‐SUPPRESSOR CELL ACTIVITY IN GRAVES’DISEASE
Author(s) -
PACINI FURIO,
DeGROOT LESLIE J.
Publication year - 1983
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1983.tb03206.x
Subject(s) - pokeweed mitogen , medicine , endocrinology , suppressor , antibody , radioimmunoassay , t cell , immune system , biology , immunology , concanavalin a , in vitro , biochemistry , cancer
SUMMARY Cellular interactions involved in Graves’disease were studied in patients in different stages of the disease and in normal controls. Synthesis and secretion of immunoglobulin G (IgG) in the supernate of pokeweed mitogen (PWM)‐stimulated cultures of constant numbers of non E rosette forming cells (E − cells) and of increasing numbers of autologous E rosette forming cells (E + cells) (E + /E − ratios = 1:1, 2:1, 4:1, 8:1, 10:1) were measured by a specific solid‐phase radioimmunoassay. In the normal group, the mean IgG production increased with increasing E + / E‐ ratio (T helper effect), reaching a maximum at a T/B ratio of 4:1, then decreased at higher E + /E − ratios (T suppressor effect). At a E + /E − ratio of 10:1 the IgG synthesis was 39% of the peak value. In the Graves’patients the mean IgG synthesis increased with increasing numbers of E + cells at every ratio with a peak value found at E + /E − ratio = 10:1. There was no detectable suppressor effect. In three experiments performed with allogeneic combinations of cells, it was observed that the Graves’E − cells were able to respond both to helper and suppressor signals from normal E + cells, while the Graves’E + were not able to suppress IgG synthesis by normal E − cells. Treatment of E + cells with 3,000 cGy of irradiation before adding them to E − cells abolished the suppressor effect seen at the higher E + /E − ratios in the normal controls because of inactivation of the T suppressor lymphocytes. In contrast, the same procedure was without effect on the IgG synthesis by E − cells in Graves’patients. When peripheral blood mononuclear cells (PBMC) were cultured in the presence of PWM and of PWM + Concanavalin‐A (Con‐A), the PWM‐induced synthesis of IgG was suppressed in the presence of Con‐A by 75% (using unfractionated PBMC) and 74% (using E + /E − cells) at 1:1 ratio in normal controls, while Graves’patients’cells caused lower suppression of 66 and 48%, respectively. This latter value was significantly different from that found in the normal group ( P < 0·05).