Engraftment of human lymphocytes and thyroid tissue into scid and rag2-deficient mice: absent progression of lymphocytic infiltration
| Autor: | Terry F. Davies, A. Martin, M Valentine, Pamela D. Unger, S W Yeung, L D Shultz |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
endocrine system
medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment Lymphocyte Graves' disease Clinical Biochemistry Thyroid Gland Mice SCID Biochemistry Peripheral blood mononuclear cell Thyroiditis Autoimmune Diseases Mice Endocrinology Internal medicine medicine Animals Humans Hashimoto Disease Lymphocytes Autoantibodies Mice Knockout Severe combined immunodeficiency business.industry Biochemistry (medical) Thyroid Thyroiditis Autoimmune Nuclear Proteins Proteins HLA-DR Antigens medicine.disease Thyroid Diseases Graves Disease DNA-Binding Proteins medicine.anatomical_structure Lymphocyte Transfusion Severe Combined Immunodeficiency Thyroglobulin business |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 79:716-723 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | To study human autoimmune thyroid disease in an animal model we have investigated the in vivo survival of human thyroid tissues and functionality of human lymphocytes in severe combined immunodeficient (scid) mice and recombination-activating gene (rag2) knockout mice. We found successful engraftment of human thyroid tissues in both scid and rag2-deficient mice. However, when peripheral blood mononuclear cells were transplanted ip, human immunoglobulin production was poor in rag2-deficient mice compared to that in scid mice (mean human immunoglobulin G levels at 6 weeks, 0.2 +/- 0.2 microgram/mL in two of eight rag2-deficient mice compared to 20.8 +/- 7.0 micrograms/mL in seven of nine scid mice; P < 0.05). We, therefore, only pursued the further use of scid mice and transplanted them with thyroid tissue from patients with either Graves' disease (four patients) or Hashimoto's thyroiditis (one patient). At the functional level, we observed transiently increased thyroid hormone levels (T4 peaking at 5.4 +/- 0.2 microgram/dL compared to a normal level of 2.6 +/- 0.2 microgram/dL); human autoantibodies to human thyroglobulin, human thyroid peroxidase, and the human TSH receptor were also detected in thyroid-transplanted mice. In contrast to recent reports, histological examination of the thyroid explants showed no increase in the lymphocytic infiltrate compared to the original donor tissue, nor was there any thyroid follicular destruction observed. In fact, many of the transplants demonstrated a marked diminution in the infiltrates over time, with an absence of HLA-DR antigen expression by both T-cells and thyrocytes. Cotransplanted allogeneic thyroid tissues were unremarkable in terms of lymphocytic infiltrates and showed intact morphology. Taken together, these data point to a relative degree of T-cell inactivity within the thyroid explants from the scid mouse. Hence, a factor(s) present in the patient with autoimmune thyroid disease that activates their thyroid-specific T-cells may be absent in this murine model as presently constructed. |
| Databáze: | OpenAIRE |
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