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Thymosin alpha 1-induced modulation of cellular responses and functional T-cell subsets in mice with experimental autoimmune thyroiditis. 1985

V J Tomazic, and E A Novotny, and J V Ordonez

The effects of Ta-1, a peptide constituent of thymosin fraction 5, were studied on murine autoimmune thyroiditis using two congenic strains of mice, B10.Br (Br) and B10.D2 (D2), which are sensitive and resistant to experimental autoimmune thyroiditis (EAT) induction, respectively. EAT was induced by either 2 weekly iv injections of mouse thyroglobulin with adjuvant lipopolysaccharide (LPS) or intradermal injection of thyroglobulin mixed with complete Freund's adjuvant (CFA). The criteria for induction and intensity of thyroiditis were the level of lymphoid infiltration in the thyroid gland and the titer of anti-thyroglobulin antibodies. Ta-1 was given in 5 or 10 daily sc injections in doses ranging from 0.0001 to 0.1 microgram/injection. The injections were commenced at varying intervals from the 1st to the 4th week after immunization. T-Cell subsets in the spleens were determined 2 weeks after the first antigen injection and thyroid infiltration was determined 3 weeks later. Treatment with Ta-1 between the two antigen injections increased the level of thyroiditis in resistant mice, but had no effect in sensitive mice. Treatment for the first 2 weeks had similar effects in resistant mice, but also suppressed thyroiditis in the sensitive strain. Later treatments, during the 3rd and 4th weeks after immunization also revealed immunomodulating properties of Ta-1, with a suppressing effect on thyroiditis in sensitive mice and an enhancing effect in the resistant strain. Both effects of Ta-1 were dose dependent. The effects of Ta-1 on the individual phenotypes were also dose dependent. The dose of 0.01 microgram greatly lowered the percentages of Lyt-2+3+ cells in D2 mice and mildly increased the percentages in Br mice, but did not change the Lyt-1+ cell level in either strain. On the other hand, the dose of 0.001 microgram greatly increased the percentage of Lyt-1+ cells in D2 mice and mildly decreased it in the Br strain, but did not alter the Lyt-2+3+ cell subset in either strain. Thus, both doses of Ta-1 modulated Lyt-1+/2+3+ ratios, with each dose affecting a different T-cell subset. The changes in the response to thyroglobulin are apparently exerted through the regulation of the functional T-cell subset balance.

UI MeSH Term Description Entries
D007111 Immunity, Cellular Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Cell-Mediated Immunity,Cellular Immune Response,Cell Mediated Immunity,Cell-Mediated Immunities,Cellular Immune Responses,Cellular Immunities,Cellular Immunity,Immune Response, Cellular,Immune Responses, Cellular,Immunities, Cell-Mediated,Immunities, Cellular,Immunity, Cell-Mediated,Response, Cellular Immune
D007114 Immunization Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). Immunologic Stimulation,Immunostimulation,Sensitization, Immunologic,Variolation,Immunologic Sensitization,Immunological Stimulation,Sensitization, Immunological,Stimulation, Immunologic,Immunizations,Immunological Sensitization,Immunological Sensitizations,Immunological Stimulations,Sensitizations, Immunological,Stimulation, Immunological,Stimulations, Immunological,Variolations
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000077596 Thymalfasin A thymus hormone polypeptide found in thymosin fraction 5 (a crude thymus gland extract) but now produced by synthesis. It is used alone or with interferon as an immunomodulator for the treatment of CHRONIC HEPATITIS B and HEPATITIS C. Thymalfasin is also used for the treatment of chemotherapy-induced immunosuppression, and to enhance the efficacy of influenza and hepatitis B vaccines in immunocompromised patients. Thymosin alpha(1),Thymosin alpha1,Zadaxin,alpha1-Thymosin,alpha1 Thymosin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D013947 Thymosin Thymosin. A family of heat-stable, polypeptide hormones secreted by the thymus gland. Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging. Thymosin Fs,Thymosins
D013967 Thyroiditis, Autoimmune Inflammatory disease of the THYROID GLAND due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-CELLS and thyroid AUTOANTIBODIES. The clinical signs can range from HYPOTHYROIDISM to THYROTOXICOSIS depending on the type of autoimmune thyroiditis. Autoimmune Thyroiditis,Thyroiditis, Lymphocytic,Thyroiditis, Lymphomatous,Autoimmune Thyroiditides,Lymphocytic Thyroiditides,Lymphocytic Thyroiditis,Lymphomatous Thyroiditides,Lymphomatous Thyroiditis,Thyroiditides, Autoimmune,Thyroiditides, Lymphocytic,Thyroiditides, Lymphomatous

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