The regulatory role of human helper T-cell clones on antithyroid antibody production by peripheral B-cells.
The helper effects of thyroid antigen-specific T-cell clones (TCC) on antibody production by peripheral B-cells were studied and compared with similar effects of self major histocompatibility complex II (MHC-II)-reactive TCC as well as uncloned CD4+ cells. Ten TCC were derived from thyroid tissue or peripheral blood mononuclear cells (PBMC) in patients with Graves' disease. Uncloned CD4+ cells were also obtained from PBMC in patients with autoimmune thyroid disease. All TCC were CD3+/CD4+. B-Cells from patients with mainly high serum levels of microsomal antibodies (McAb) were cultured alone and with either TCC or uncloned CD4+ cells in the presence or absence of thyroid antigens [microsomal antigen/thyroid peroxidase (McAg/TPO) and thyroglobulin (Tg)] or pokeweed mitogen (PWM). Total immunoglobulin G (IgG) and specific thyroid antibodies were measured by enzyme-linked immunosorbent assay. Self MHC-II-reactive TCC induced B-cell production of total IgG and even McAb independent of antigens or PWM. Specific TCC required thyroid antigens to induce antibodies. The optimal McAg/TPO or Tg concentration was 10 ng/mL for total IgG production and 1 ng/mL McAg/TPO for McAb synthesis. The addition of PWM did not affect McAb production, but enhanced total IgG synthesis by B-cells under the influence of some specific TCC. Uncloned CD4+ cells induced both total IgG and McAb synthesis in the presence of PWM. With thyroid antigens, uncloned CD4+ cells induced total IgG synthesis at levels comparable to those of specific TCC, but induced smaller quantities of McAb in the presence of McAg/TPO. Our antigen-specific TCC could, therefore, stimulate specific B-cells to produce thyroid antibodies in vitro. Self MHC-II-reactive TCC could also induce specific antibodies by B-cells. Both self MHC-II-reactive CD4+ cells and antigen-specific CD4 cells may play an important role in the pathogenesis and/or perpetuation of autoimmune thyroid disease.
Department of Medicine, University of Chicago, Illinois 60637.
M E
ME
Fisfalen
K
K
Soltani
A M
AM
Janiga
Y
Y
Kawakami
E
E
Macchia
J
J
Quintans
L J
LJ
DeGroot
D000906:Antibodies / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells / Q000502:physiology; D000939:Epitopes; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008934:Mitogens / Q000494:pharmacology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology
D000906:Antibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D008934:Mitogens