Original Paper Int Arch Allergy Immunol 1992;98:317-323
Departments of a Medicine and b Pathology, Mount Sinai School of Medicine. New York, N.Y., USA: c The Jackson Laboratory, Bar Harbor, Me., USA
Key Words Autoantibodies Autoimmune (Hashimoto’s) thyroiditis Autoimmune thyroid disease seid mouse B cells T cells Transplantation
Supported in part by Public Health Service grants DK28242 and DK35674 from NIDDKD (to TFD) and grant A130389 from NIAID (to LS). and the Charles H. Revson Foundation (to AM). TFD is the Theodore and Florence Baumrittcr Professor of Medicine.
Characteristics of Long-Term Human Thyroid Peroxidase Autoantibody Secretion in scid Mice Transplanted with Lymphocytes from Patients with Autoimmune Thyroiditis
Abstract We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thy roid peroxidase (hTPO) autoantibodies. Patient’s peripheral blood mononu clear cells (PBMC) were transplanted into scid mice via intraperitoneal in jections and human immunoglobulin G (hlgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after trans plantation. Human IgG reached maximum serum levels of >3,000 pg/ml (mean ±SEM = 1,199 ±354 pg/ml) after an average of 6.5 weeks. In reconsti tuted mice (hereafter named At-Scid-hu) substantial titers of anti-hTPO of up to 0.51 (ELISA index, normal range < 0.02) were observed over a period of 1-2 months, followed by a gradual decline. Immunization of AT-Scid-hu mice with immunogenic, recombinant human hTPO (rec-hTPO) failed to enhance hTPO-Ab levels. Furthermore, there was no correlation between the magni tude of human IgG in the murine serum and concomitant levels of anti-hTPO. Murine thyroid function was unaffected by the transplantation of PBMC, as evidenced by normal scrum thyroxine (T4) levels, and lack of specific path ologic changes in the thyroid. These data indicate, for the first time, the poten tial for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory fac tors inpinging on the human B cells surviving in the murine environment. In addition, the hlgG levels achived in AT-Scid-hu mice were significantly higher than in scid mice reconstituted with immune cells from patients with Graves’ disease, thus suggesting a difference in the overall reactivity of immune cells in patients with these different forms of autoimmune thyroid disease.
Correspondence to: Dr. A. Martin Box 1055 Mount Sinai Medical Center 100th St A 5th Ave New York. NY 10029 (USA)
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 10:03:25 AM
Andreas Martin3 Hironori Kimura3 Swan Thungb Po Fong3 Leonard D. Shultzc Terry F. Davies3
Table 1. Thyroid autoantibodies in PBMC donors
Autoimmune (1) EDE (2) MCC (3) HIR (4) POL Mean ±SEM
Age Sex years
Treatment
thyroiditis patients 42 f T4 52 f T4 57 f T4 50 f T4 50 ± 3
Graves’ disease patients [6] Mean ± SEM Normal range of human El
Autoantibody levels anti-hTg
anti-hTPO
0.45 1.70
Departments of a Medicine and b Pathology, Mount Sinai School of Medicine. New York, N.Y., USA: c The Jackson Laboratory, Bar Harbor, Me., USA
Key Words Autoantibodies Autoimmune (Hashimoto’s) thyroiditis Autoimmune thyroid disease seid mouse B cells T cells Transplantation
Supported in part by Public Health Service grants DK28242 and DK35674 from NIDDKD (to TFD) and grant A130389 from NIAID (to LS). and the Charles H. Revson Foundation (to AM). TFD is the Theodore and Florence Baumrittcr Professor of Medicine.
Characteristics of Long-Term Human Thyroid Peroxidase Autoantibody Secretion in scid Mice Transplanted with Lymphocytes from Patients with Autoimmune Thyroiditis
Abstract We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thy roid peroxidase (hTPO) autoantibodies. Patient’s peripheral blood mononu clear cells (PBMC) were transplanted into scid mice via intraperitoneal in jections and human immunoglobulin G (hlgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after trans plantation. Human IgG reached maximum serum levels of >3,000 pg/ml (mean ±SEM = 1,199 ±354 pg/ml) after an average of 6.5 weeks. In reconsti tuted mice (hereafter named At-Scid-hu) substantial titers of anti-hTPO of up to 0.51 (ELISA index, normal range < 0.02) were observed over a period of 1-2 months, followed by a gradual decline. Immunization of AT-Scid-hu mice with immunogenic, recombinant human hTPO (rec-hTPO) failed to enhance hTPO-Ab levels. Furthermore, there was no correlation between the magni tude of human IgG in the murine serum and concomitant levels of anti-hTPO. Murine thyroid function was unaffected by the transplantation of PBMC, as evidenced by normal scrum thyroxine (T4) levels, and lack of specific path ologic changes in the thyroid. These data indicate, for the first time, the poten tial for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory fac tors inpinging on the human B cells surviving in the murine environment. In addition, the hlgG levels achived in AT-Scid-hu mice were significantly higher than in scid mice reconstituted with immune cells from patients with Graves’ disease, thus suggesting a difference in the overall reactivity of immune cells in patients with these different forms of autoimmune thyroid disease.
Correspondence to: Dr. A. Martin Box 1055 Mount Sinai Medical Center 100th St A 5th Ave New York. NY 10029 (USA)
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 10:03:25 AM
Andreas Martin3 Hironori Kimura3 Swan Thungb Po Fong3 Leonard D. Shultzc Terry F. Davies3
Table 1. Thyroid autoantibodies in PBMC donors
Autoimmune (1) EDE (2) MCC (3) HIR (4) POL Mean ±SEM
Age Sex years
Treatment
thyroiditis patients 42 f T4 52 f T4 57 f T4 50 f T4 50 ± 3
Graves’ disease patients [6] Mean ± SEM Normal range of human El
Autoantibody levels anti-hTg
anti-hTPO
0.45 1.70
