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 thyroid disease (AITD), we have examined the in vitro and in vivo effects of a monoclonal antibody (mAb) against with CD45RB, termed MT3. MT3 was added to cultured peripheral blood mononuclear cells (PBMC) from patients with AITD and was additionally injected into severe combined immunodeficient (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 cultured for 7 days, the stimulation index [SI: counts per minute (cpm) with mAb/cpm without mAb] was lowered by MT3 in NC and GD patients. However, the mean SI was not lowered in patients with HT. In SCID mice, the concentrations of human immunoglobulin G, antithyroglobulin and antithyroperoxidase antibodies in sera were not significantly changed by injecting MT3. The expression of human leukocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1 on engrafted human thyrocytes 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006111:Graves Disease / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000637:transplantation; D013961:Thyroid Gland / Q000737:chemistry / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens