EFFECTS OF MONOCLONAL-ANTIBODY AGAINST CD45RB ON PERIPHERAL-BLOOD MONONUCLEAR CELL-PROLIFERATION AND ON HLA-DR AND ADHESION MOLECULE EXPRESSION ON THYROCYTES OF PATIENTS WITH AUTOIMMUNE THYROID-DISEASE

To evaluate the role of CD45 (especially that of the ectodomain region B) on immunocyte-thyrocyte signaling in patients with autoimmune thyr oid disease (AITD), we have examined the in vitro and in vivo effects of a monoclonal antibody (mAb) against CD45RB, termed MT3, MT3 was add ed to cultured peripheral blood mononuclear cells (PBMC) from patients with AITD and was additionally injected into severe combined inmunode ficient (SCID) mice to which Graves' thyroid cells and intrathyroidal lymphocytes were engrafted, MT3 stimulated proliferation of PBMC when cultured for 2 to 3 days in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) and in normal controls (NC), However, when c ultured for 7 days, the stimulation index CSI: counts per minute (cpm) with mAb/cpm without mAb] was lowered by MT3 in NC and GD patients, H owever, the mean SI was not lowered in patients with HT, In SCID mice, the concentrations of human immunoglobulin G, antithyroglobulin and a ntithyroperoxidase antibodies in sera were not significantly changed b y injecting MT3, The expression of human leukocyte antigen (HLA)-DR an d intercellular adhesion molecule (ICAM)-1 on engrafted human thyrocyt es decreased after the tissues were engrafted into the control mice to which vehicle alone was injected, However, in the mice injected with MT3, HLA-DR and ICAM-1 expression remained high or up-regulated by the injection, These data suggest that modulation of the region B of CD45 by MT3 enhances lymphocyte proliferation; lymphocytes in HT patients may have an abnormality in CD45RB distribution and/or signal transduct ion via CD45, and CD45RB-related immunocyte-thyrocyte signaling is inv olved in HLA-DR and ICAM-1 expression on Graves' thyroid cells.