Preservation of functioning human thyroid organoids in the scid mouse. IV. In vivo selection of an intrathyroidal T cell receptor repertoire.
Antigens-CD, Gene-Expression, Graves'-Disease, Human, Mice, Mice-SCID: ph, Monocytes: ph, Organoids: ph, Polymerase-Chain-Reaction, Receptors-Antigen-T-Cell: ge, me, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: de, ph, Thyroid-Gland: de, cy, ph, Transcription-Genetic
Endocrinology 1997 Nov;138(11):4868-75
DK28242/DK/NIDDK, DK35674/DK/NIDDK, AI30389/AI/NIAID
To study the in vivo influence of thyroid cells on the T cell receptor repertoire in human autoimmune thyroid disease, we mixed lymphocyte-free thyrocytes (approximately 1.2 x 10) from patients with Graves' disease with autologous peripheral blood mononuclear cells (PBMC; approximately 1.5 x 10) and transplanted this mixture sc into scid mice while suspended in a basement membrane gel (approximately 0.4 ml). Controls included mice that received either thyrocytes only or PBMC only. The resulting artificial mixed cell thyroid organoids were explanted after 5 weeks, and their T cell receptor repertoire was examined. Of a total of 63 organoids constructed, 60 were recovered (95.2%). Total RNA was extracted and then analyzed by reverse transcription-PCR primarily for human T cell receptor (hTcR) Vbeta gene expression using 21 hTcR Vbeta amplimers. A restricted pattern of hTcR Vbeta gene expression was found, with 6 Vbeta genes (Vbeta5, 6, 7, 8, 13.1, and 18) predominantly expressed [P < 0.05, by ANOVA on ranks and Student-Newman-Keul's (SNK) test]. PBMC and control organoids showed no preferential selection of particular hTcR V gene-expressing T cells. This reductionist, mixed cell, thyroid model reflected earlier observations in human and murine autoimmune thyroid diseases in which a bias in hTcR V gene family expression had been observed. The model permitted in vivo T cell selection and/or enrichment of potentially disease relevant human T cells.
Martin, A; Matsuoka, N; Zhang, J; Zhou, A; Nakashima, M; Unger, P; Schwartz, A E.; Friedman, E W.; Shultz, L D.; and Davies, T F., " Preservation of functioning human thyroid organoids in the scid mouse. IV. In vivo selection of an intrathyroidal T cell receptor repertoire." (1997). Faculty Research 1990 - 1999. 931.