title: In vitro induction of anti-thyroid microsomal antibody-secreting cells in peripheral blood mononuclear cells from normal subjects.
abstract: Secretion of immunoglobulin G (IgG) and IgM antithyroid microsomal antibodies (AMA) was induced in vitro by coculturing non-T cells (B lymphocytes) and autologous CD4 (helper/inducer) cells from normal subjects stimulated with pokeweed mitogen (PWM) or a combination of human thyroid microsomal antigen (McAg) and Staphylococcus aureus Cowan I (SAC) strain. With PWM stimulation, AMA production was induced in more IgM-secreting cells (AMA-M) than IgG-secreting cells (AMA-G). However, McAg plus SAC stimulation resulted in similar numbers of AMA-G- and AMA-M-secreting cells. PWM induced a significantly greater number of both AMA-M (and generalized IgM)-secreting cells than did McAg plus SAC, while the number of AMA-G-secreting cells induced by the two stimuli were similar. There were no significant differences between autologous or allogeneic CD4 cells from normal subjects or patients with autoimmune thyroid disease (AITD) when cocultured with B cells from normal subjects in terms of helper activity in the induction of AMA-M- or IgM-secreting cells with PWM stimulation. However, with McAg plus SAC, CD4 cells from patients with AITD induced a significantly greater number of AMA-M-secreting cells than did autologous or allogeneic CD4 cells from normal subjects. There was no difference in helper activity between autologous and allogeneic normal CD4 cells in the induction of generalized IgM-secreting cells regardless of the stimulus used. Normal autologous or allogeneic CD8 (suppressor/cytotoxic) cells cocultured with normal B cells and autologous CD4 cells suppressed the induction of AMA-M-secreting cells by PWM stimulation. On the other hand, CD8 cells from patients with AITD suppressed the induction of AMA-M-secreting cells significantly less effectively. All CD8 cells suppressed the induction of IgM-secreting cells equally well. We conclude that 1) B lymphocytes from normal subjects are capable of producing autoantibodies in vitro in the presence of CD4 cells; 2) the helper activity of CD4 cells from patients with AITD to induce AMA-M secreting cells is greater than that of normal CD4 cells with thyroid antigen stimulation; and 3) this helper activity may be due to relatively impaired suppressor activity in thyroid antigen-specific CD8 cells from patients with AITD, whereas the immunoregulatory function of CD8 cells from normal subjects appears to play an important role in the maintenance of self-tolerance.
authors.affiliation: Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Iitaka
authors.forename: J F
authors.initials: JF
authors.lastname: Aguayo
authors.forename: Y
authors.initials: Y
authors.lastname: Iwatani
authors.forename: V V
authors.initials: VV
authors.lastname: Row
authors.forename: R
authors.initials: R
authors.lastname: Volpé
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008861:Microsomes / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013959:Thyroid Diseases / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M