title: The SCID-hu mouse and thyroid autoimmunity: characterization of human thyroid autoantibody secretion.
abstract: Severe combined immunodeficient (SCID) mice were injected with peripheral blood mononuclear cells (PBMC) from normal individuals and 14 out of 18 had detectable serum human (h) IgG (maximum levels providing a mean +/- SEM 934 +/- 213 micrograms/ml) and IgM (253 +/- 93 micrograms/ml) at 3-6 weeks after transplantation. Serum human immunoglobulin levels were maximum 6-12 weeks after transplantation and declined to low levels over the subsequent 5 months. Human B cells constituted up to 10% and human T cells up to 40% of cells in the peripheral circulation and spleens of these animals 2-3 weeks after transplantation, PBMC, or intrathyroidal (IT) lymphocytes, from 6 patients with Graves' disease and high serum levels of thyroid autoantibodies were transplanted into 30 SCID mice (Graves' SCID-hu). Although serum human immunoglobulins were observed in only low amounts in the animals receiving IT lymphocytes (n = 4), increased levels of hIgG or hIgM were more easily detectable in 19 Graves' SCID-hu mice that received PBMC. The Graves' SCID-hu mice had significantly lower mean levels of hIgG and hIgM than those observed following transplantation of normal PBMC (mean maximum 328 +/- 113 and 32 +/- 21 micrograms/ml, respectively). Six of these 19 mice had detectable human autoantibody to thyroid peroxidase (TPO, as microsomal antigen) between 3 and 8 weeks after transplantation, with titers ranging from 0.05 to 0.39 (normal SCID-hu serum less than 0.02 ELISA Index). No abnormal thyroid hormone (T4 and T3) levels or thyroiditis was seen when compared to normal SCID-hu mice. Immunization of reconstituted SCID mice with recombinant immunoactive human TPO antigen failed to initiate anti-TPO in normal PBMC-treated mice nor did it increase the titer of human anti-TPO in the anti-TPO positive animals. In conclusion we successfully established human thyroid autoantibody secretion in the SCID-hu mouse and characterized the transient nature of the model. Further studies will be required to achieve successful antigen presentation in this system.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: P
authors.initials: P
authors.lastname: Fong
authors.forename: D
authors.initials: D
authors.lastname: Kendler
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: S
authors.initials: S
authors.lastname: Thung
authors.forename: A
authors.initials: A
authors.lastname: Martin
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D016026:Bone Marrow Transplantation / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013961:Thyroid Gland / Q000276:immunology*; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine