Graves' disease thyroid tissue transplants in scid mice: persistent selectivity in hTcR Va gene family use.
We have analyzed the human T-cell receptor (hTcR) V alpha gene repertoire in thyroid tissue transplants of a patient with hyperthyroid Graves' disease. Blocks of thyroid tissue were transplanted subcutaneously into 10 mice with severe immunodeficiency (scid) and 4 weeks later 5 of the mice were injected intraperitoneally with autologous peripheral blood mononuclear cells (PBMC) (10(7) cells per mouse). After a further 3 weeks, mice were sacrificed and total cellular RNA and cDNA prepared from each of the explants. We used specific olingonucleotides in polymerase chain reactions (PCR) to amplify 18 different human hTcR V alpha gene families and the identity of the PCR fragments was confirmed by Southern blot analysis. Different samples of the donor thyroid tissue consistently expressed 9-10 of the 18 hTcR V alpha gene families screened (V alpha 1-7, 11, 12 & 15). A more marked bias in hTcR V gene family use was seen in each of the explants with a mean of only 2.8 V alpha gene families detected. After 7 weeks of transplantation, the thyroid explants largely reflected some of the same genes seen in the hTcR V gene repertoire of the donor tissue with particularly pronounced expression of V alpha 2 and V alpha 3 gene families. The transplantation of PBMC into the scid mice showed evidence for their accumulation within the transplanted thyroid tissues as judged by the appearance of additional hTcR V gene families expressed in these samples although the specificity of such accumulation remains unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
De Riu
S
S
Division of Endocrinology and Metabolism, Mount Sinai School of Medicine, New York 10029, USA.
Martin
A
A
Valentine
M
M
Concepcion
E S
ES
Shultz
L D
LD
Davies
T F
TF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000276:immunology; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000302:isolation & purification; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*
D016693:Receptors, Antigen, T-Cell, alpha-beta