Cell-mediated immunity in the exophthalmos of graves’ disease as demonstrated by the migration inhibition factor (MIF) test

The production of migration inhibition factor (MIF) by sensitized lymphocytes in the presence of specific antigen is an accepted in vitro test of cell-mediated immunity (CMI). The MIF test has been performed in patients with untreated Graves' disease (6 patients with hyperthyroidism and exophthalmos, 9 patients with hyperthyroidism but no exophthalmos, and 9 patients with Euthyroid Ophthalmic Graves' disease) and in normal subjects, against human retroorbital muscle antigen (RMA), thyroid antigen (TA) and other organ antigens. Human thyrotrophin (TSH) was also used as an antigen, either alone, or after incubation with RMA. All patients with exophthalmos (whether hyperthyroid or euthyroid) showed positive MIF to RMA. A positive MIF to RMA was also found in 1/3 of the hyperthyroid patients without exophthalmos; the remainder however did not show MIF to this antigen. All hyperthyroid patients showed a positive MIF to TA (unrelated to the presence or absence of exophthalmos). In the euthyroid patients with exophthalmos, 2/3 also showed positive MIF to TA, but the remainder were negative; in this group, there was a very good correlation between the results of the MIF test (to TA) and evidence of thyroid dysfunction. There was no MIF against TSH in any of the groups studied, nor did TSH enhance the antigenicity of RMA. These studies indicate the presence of CMI in the exophthalmos of Graves' disease. Since MIF to RMA does not correlate well with MIF to TA, it may be suggested that antigenic dissimilarity exists between RMA and TA; this implies that different populations of lymphocytes may be involved in exophthalmos as opposed to hyperthyroidism, which thus perhaps should be regarded as separate entities.