Faculty Research 1990 - 1999

Graves' disease thyroid tissue transplants in scid mice: persistent selectivity in hTcR Va gene family use.

Document Type

Article

Publication Date

1994

Keywords

Animal, Base-Sequence, Gene-Expression-Regulation: im, Graves'-Disease: im, pa, Human, Mice, Mice-SCID, Molecular-Sequence-Data, Polymerase-Chain-Reaction, Receptors-Antigen-T-Cell-alpha-beta: ge, SUPPORT-U-S-GOVT-P-H-S, Thyroid-Gland: im, me, tr

First Page

271

Last Page

277

JAX Source

Autoimmunity 1994;19(4):271-7

Grant

DK28242/DK/NIDDK, DK35674/DK/NIDDK, AI30389/AI/NIAID

Abstract

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)

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