F. Akasu et al., RECONSTITUTION OF SEVERE COMBINED IMMUNODEFICIENT MICE WITH INTRATHYROIDAL LYMPHOCYTES OF THYROID XENOGRAFTS FROM PATIENTS WITH HASHIMOTO THYROIDITIS, The Journal of clinical endocrinology and metabolism, 76(1), 1993, pp. 223-230
Thyroid tissues from patients with Hashimoto's thyroiditis (HT) have b
een xenografted to both severe combined immunodeficiency (SCID) mice a
nd nude mice to study the intrathyroidal lymphocytes which were expect
ed to migrate from the xenografts in the SCID mice. Peripheral blood m
ononuclear cells from HT, Graves' disease, and normal donors have also
been separately engrafted. SCID mice, but not nude mice with HT thyro
id grafts produce human immunoglobulins. More immunoglobulin G (IgG),
but less IgM and IgA is produced in SCID mice with HT thyroid grafts (
SCID-TH), compared to SCID mice injected with peripheral blood mononuc
lear cells from patients with HT or normal donors (SCID-PB), suggestin
g that different B cell subpopulations were active in the SCID-PB vs.
SCID-TH. Production of IgG by SCID-PB and SCID-TH was maintained 6 wee
ks after engraftment, and decreased thereafter. SCID mice but not nude
mice grafted with HT thyroid tissue produce antibodies to thyroglobul
in and thyroperoxidase. Lymphocytes within intact HT thyroid grafts pe
rsist in SCID mice, and migrate to the spleen, whereas human lymphocyt
es do not survive in the thyroid grafts or other tissues of the nude m
ouse. In 6 weeks, the xenografts in nude mice became histologically no
rmal. In contrast, xenografts from SCID mice showed more marked inflam
matory changes than in the original human lesion, although the ratio o
f T/B cells is unchanged. This worsening of the lesion may relate to t
he increase in activation of the T-lymphocytes.