Characteristics of long-term human thyroid peroxidase autoantibody secretion in scid mice transplanted with lymphocytes from patients with autoimmune thyroiditis.
We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thyroid peroxidase (hTPO) autoantibodies. Patient's peripheral blood mononuclear cells (PBMC) were transplanted into scid mice via intraperitoneal injections and human immunoglobulin G (hIgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after transplantation. Human IgG reached maximum serum levels of > 3,000 micrograms/ml (mean +/- SEM = 1,199 +/- 354 micrograms/ml) after an average of 6.5 weeks. In reconstituted 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 magnitude 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 serum thyroxine (T4) levels, and lack of specific pathologic changes in the thyroid. These data indicate, for the first time, the potential for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory factors inpinging on the human B cells surviving in the murine environment.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
A
A
Department of Medicine, Mount Sinai School of Medicine, New York, N.Y.
Kimura
H
H
Thung
S
S
Fong
P
P
Shultz
L D
LD
Davies
T F
TF
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016219:Immunotherapy, Adoptive; D007453:Iodide Peroxidase / Q000276:immunology*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D013997:Time Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D007453:Iodide Peroxidase