Evidence for antigen presentation to sensitized T cells by thyroid peroxidase (TPO)-specific B cells in mice injected with fibroblasts co-expressing TPO and MHC class II

Injection of AKR/N mice with fibroblasts co-expressing MHC class II and TPO in the absence of adjuvant induces IgG-class TPO antibodies that resemble spontaneously arising human thyroid autoantibodies. We have used this model to examine the effect of iodide on TPO antibody induction as well as to an alyse the interaction between T and B cells. Despite its importance as a ma jor environmental factor in thyroid autoimmunity, variable iodide intake ha d no detectable effects on TPO antibody levels, lymphocytic infiltration of the thyroid or thyroid hormone levels. In terms of T cell responsiveness, splenocytes from TPO fibroblast-injected mice, but not from control mice, p roliferated in response to TPO. Intriguingly, B cell-depleted splenocytes ( mainly T cells without reduction of macrophages) proliferated in response t o TPO only when co-cultured with irradiated autologous splenocytes from TPO fibroblast-injected mice but not from control mice. These data suggest tha t TPO-specific B cells are involved in antigen presentation to sensitized T cells and are supported by the ability of spleen cells from TPO cell-injec ted (but not control) mice to secrete TPO antibodies spontaneously in cultu re. In conclusion, we provide the first evidence for the presence of thyroi d autoantigen-specific B cells and their ability to present their autoantig en to sensitized T cells in mice induced to develop TPO antibodies resembli ng autoantibodies in humans.