A delayed-type hypersensitivity skin-test system using the insulinoma cell line RINm5F to monitor beta cell-specific cellular autoimmune reactivity in the spontaneously diabetic BB/O rat.

Islet-specific autoimmune reactivity (humoral and cell-mediated) is the basis for the insulitis process of type I diabetes mellitus. In this report a delayed-type hypersensitivity (DTH) skin test was used to monitor the presence of an islet-specific cell-mediated autoimmune component in BB/O rats. The BB/O rat is a strain characterized by the spontaneous development of type I diabetes. Intact RINm5F cells as well as a RINm5F cell membrane preparation were used as DTH skin test antigens. Rats of different ages and disease stages were tested in the ear with the insulinoma cell line and its cell membrane preparation. As control antigens, the fibroblast cell line 3Y1 and a cell membrane preparation made thereof were used. The DTH reaction system showed a positive cell-mediated reactivity in BB/O rats for membrane-bound RINm5F cell antigens, and not for the control fibroblast 3Y1 cell membrane determinants. The true DTH character of the skin test was established by the time-course of the reaction (maximum at 24 h), the histopathology (infiltration by dendritic cells, lymphocytes and macrophages), and the possibility to transfer the reaction with spleen cells and lymph node cells. The DTH test towards RINm5F cells showed the highest prevalence of positivity (100%) in BB/O rats around the onset of diabetes (3 weeks before to 3 weeks after the onset of glucosuria). The prevalence of DTH positivity was 56% in the period of more than 3 weeks before the onset of glucosuria. In BB/O rats with a duration of glucosuria of more than 3 weeks, the prevalence of positivity was around 60-70%.

Dendritic cells and class II MHC expression on thyrocytes during the autoimmune thyroid disease of the BB rat.

The BB rat is a well-established model for spontaneous thyroid autoimmune disease. Since antigen presentation in thyroid autoimmunity is still a matter of debate, we studied the presence of antigen-presenting dendritic cells in the thyroid of the BB/O rat during the development of the disease in relation to the presence of other leucocytes and the aberrant expression of class II MHC determinants by thyrocytes. Thyroid glands, as well as thyroid-draining lymph nodes, were investigated in enzyme histochemistry and immune histochemistry. The appearance of anti-colloid antibodies in the circulation at 6 weeks of age was accompanied by an increase in the weight of the thyroid-draining cervical lymph nodes, which contained many anti-thyroglobulin-producing plasma cells. The only noteworthy event in the thyroid gland in this early stage of the disease was an increase in the number of dendritic cells. T cells, B cells, and plasma cells were virtually absent from the thyroid, and thyrocytes were invariably negative for class II MHC determinants. Only after 18 weeks of age, when large accumulations of dendritic cells, B lymphocytes, and T lymphocytes were seen in 40% of the BB thyroids, could some class II MHC positive thyroicytes be observed. At this stage the thyroid also contained some anti-thyoglobulin-producing plasma cells. Our observations suggest that dendritic cells play a role in antigen presentation in the early stages of the thyroid autoimmune response.

The goitre of the BB/O rat: an animal-model for studying the role of immunoglobulins stimulating growth of thyroid cells.

The BB rat is a well-known animal model for the study of autoimmune thyroid disease. Antithyroglobulin antibodies can be detected in the circulation from the age of 6 weeks onwards, and accumulations of lymphoid cells occurs in the thyroid of up to 60% of animals at the age of 20 weeks and over. The rat, however, stays euthyroid, the thyroid is not destroyed, and hence the disease is not yet well characterized. The study reported here shows that the thyroid weights of 41% (40/97) BB rats were raised from week 6 onwards in comparison to those of Wistar controls. Morphologically, BB thyroids showed a strong similarity to the human disease entity 'colloid goitre', namely an active growth, high columnar epithelium, branching and budding of thyrocytes, no signs of thyroid destruction and in 42% of rats at the age of 22-26 weeks, a development of intrathyroidal lymphoid tissue. Plasma TSH was not significantly raised in the animals. For this reason the presence of immunoglobulins which stimulate the growth of thyroid cells (so-called TGI's) was determined in 12-16-week-old BB rats (n = 10) and in control Wistar rats (n = 10). At this time a significant difference could be recorded in thyroid weights between BB/O rats and Wistar controls (20.1 +/- 6.0 mg vs. 15.8 +/- 2.9 mg, respectively), even in the absence of any intrathyroidal lymphoid cell infiltration. Protein-A-Sepharose purified serum IgG of these animals was used to detect TGI-activity via the 'Feulgen Cytochemical Bioassay'. Of the BB/O rats, eight were clearly positive for TGI, all of the Wistar rats were negative. The data show that the autoimmune prone BB rat may thus serve as an animal model for euthyroid goitre associated with thyroid stimulating antibodies.