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The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL)2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 hybrids and backcrosses of the autoimmune OS B15B15 with healthy inbred CB B12B12 chickens. OS-like T cell hyperproliferation and IL2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the OS to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OS-specific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related.

Thyroglobulin-binding lymphoid cells were identified in the spleen of Obese strain (DS) chickens by their capacity to form rosettes with thyroglobulin-coated chicken red blood cells. The nature of these cells was studied in inhibition experiments using turkey anti-chicken bursa or thymus cell sera and rabbit antisera specific for chicken Ig, gamma, mu, alpha, Fabgamma or Fcgamma. Spleen cells actively synthesizing surface receptors for thyroglobulin were identified as B cells and the receptors found to be complete IgM molecules. Normal T cells became thyroglobulin-rosette-forming cells via passive adsorption of thyroglobulin antibodies, a phenomenon which could be inhibited competitively by the addition of normal chicken serum to the incubation medium. Thyroglobulin antibodies passively adsorbed onto the surface of normal T cells also belong to the IgM class as verified both by inhibition experiments and studies employing IgM and IgG fractions of a high titered OS serum for the preincubation of the cell suspensions. Only preincubation with the IgM fraction of the anti-thyroglobulin antibodies resulted in the formation of significant numbers of passive rosette-forming cells.

A monoclonal antibody (INN-CH-16) was prepared which reacts with a cell surface antigen termed chicken activated T lymphocyte antigen. This antigen is expressed on antigen- or mitogen-activated T lymphocytes and is not present on nonstimulated lymphocytes. It has an apparent molecular mass of 48-50 kDa under reducing conditions. The value of this antibody for the immunohistochemical characterization of infiltrating cells in the thyroid glands from Obese strain chickens with spontaneous thyroiditis is demonstrated.