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Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras.
Clin Immunol Immunopathol. 1997 Dec; 85(3):253-64.CI

Abstract

To study the role of Th0 and Th1 cells in autoimmune thyroid disease, thyroid tissues from patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and colloid nodular disease were xenografted into SCID mice, followed by ip injection of peripheral blood mononuclear cells (PBMC), T cell lines, and T cell clones (TCC). The antigen-specific TCC reactive to TSH receptor (TSH-R), thyroid peroxidase (TPO), or thyroglobulin (Tg), and their respective peptides, were classified into Th0 (secreting IL-4 and/or IL-5 and IFN-gamma) and Th1 (secreting IFN-gamma) according to their cytokine profile. Engraftment of autologous or HLA-matched allogeneic CD4+ thyroid-specific clones with Th0 or Th1 phenotypes induced the production of total IgG and thyroid-specific autoantibodies by B cells present in xenografted thyroid tissues. TSH-R-specific clones mainly enhanced thyroid-stimulating antibodies (TSAb) production, while clones reactive to TPO and Tg increased the synthesis of TPO and Tg autoantibodies. Total IgG production, but not TSAb, was also stimulated by PBMC and TSH-R lines. TSAb correlated with the viability and hyperplasia of thyroid follicles, but not with the serum T3 levels, which were normal. Thyroid tissue viability was maintained or increased by antigen-specific Th0 clones, and decreased by Th1 clones reactive to TSH-R or TPO. Thyroid lymphocytic infiltration was variable; however, Th0 and Th1 clones from HT patients caused high degree of lymphocytic infiltration compared to the control groups. These results demonstrate for the first time that T cells clones reactive to specific epitopes of TSH-R, TPO, or Tg can generate antibody-mediated and/or cell-mediated responses in the xenografted thyroid tissue microenvironment. Such effects depend on clonal specificity, HLA class II restriction, and cytokine profile of the clone. Th0 clones reactive to TSH-R stimulate both total IgG production and TSAb in SCID mice engrafted with thyroid tissue from GD patients. Th0 and Th1 clones specific for TPO and Tg also function as helper T cells, stimulating total IgG synthesis and autoantibodies against TPO and Tg. Th1 clones may also cause tissue destruction in GD and HT.

Authors+Show Affiliations

Department of Medicine, University of Chicago, Illinois 60637, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9400625

Citation

Fisfalen, M E., et al. "Evaluating the Role of Th0 and Th1 Clones in Autoimmune Thyroid Disease By Use of Hu-SCID Chimeras." Clinical Immunology and Immunopathology, vol. 85, no. 3, 1997, pp. 253-64.
Fisfalen ME, Soltani K, Kaplan E, et al. Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras. Clin Immunol Immunopathol. 1997;85(3):253-64.
Fisfalen, M. E., Soltani, K., Kaplan, E., Palmer, E. M., van Seventer, G. A., Straus, F. H., Diaz, M., Ober, C., & DeGroot, L. J. (1997). Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras. Clinical Immunology and Immunopathology, 85(3), 253-64.
Fisfalen ME, et al. Evaluating the Role of Th0 and Th1 Clones in Autoimmune Thyroid Disease By Use of Hu-SCID Chimeras. Clin Immunol Immunopathol. 1997;85(3):253-64. PubMed PMID: 9400625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras. AU - Fisfalen,M E, AU - Soltani,K, AU - Kaplan,E, AU - Palmer,E M, AU - van Seventer,G A, AU - Straus,F H, AU - Diaz,M, AU - Ober,C, AU - DeGroot,L J, PY - 1997/12/24/pubmed PY - 1997/12/24/medline PY - 1997/12/24/entrez SP - 253 EP - 64 JF - Clinical immunology and immunopathology JO - Clin. Immunol. Immunopathol. VL - 85 IS - 3 N2 - To study the role of Th0 and Th1 cells in autoimmune thyroid disease, thyroid tissues from patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and colloid nodular disease were xenografted into SCID mice, followed by ip injection of peripheral blood mononuclear cells (PBMC), T cell lines, and T cell clones (TCC). The antigen-specific TCC reactive to TSH receptor (TSH-R), thyroid peroxidase (TPO), or thyroglobulin (Tg), and their respective peptides, were classified into Th0 (secreting IL-4 and/or IL-5 and IFN-gamma) and Th1 (secreting IFN-gamma) according to their cytokine profile. Engraftment of autologous or HLA-matched allogeneic CD4+ thyroid-specific clones with Th0 or Th1 phenotypes induced the production of total IgG and thyroid-specific autoantibodies by B cells present in xenografted thyroid tissues. TSH-R-specific clones mainly enhanced thyroid-stimulating antibodies (TSAb) production, while clones reactive to TPO and Tg increased the synthesis of TPO and Tg autoantibodies. Total IgG production, but not TSAb, was also stimulated by PBMC and TSH-R lines. TSAb correlated with the viability and hyperplasia of thyroid follicles, but not with the serum T3 levels, which were normal. Thyroid tissue viability was maintained or increased by antigen-specific Th0 clones, and decreased by Th1 clones reactive to TSH-R or TPO. Thyroid lymphocytic infiltration was variable; however, Th0 and Th1 clones from HT patients caused high degree of lymphocytic infiltration compared to the control groups. These results demonstrate for the first time that T cells clones reactive to specific epitopes of TSH-R, TPO, or Tg can generate antibody-mediated and/or cell-mediated responses in the xenografted thyroid tissue microenvironment. Such effects depend on clonal specificity, HLA class II restriction, and cytokine profile of the clone. Th0 clones reactive to TSH-R stimulate both total IgG production and TSAb in SCID mice engrafted with thyroid tissue from GD patients. Th0 and Th1 clones specific for TPO and Tg also function as helper T cells, stimulating total IgG synthesis and autoantibodies against TPO and Tg. Th1 clones may also cause tissue destruction in GD and HT. SN - 0090-1229 UR - https://www.unboundmedicine.com/medline/citation/9400625/Evaluating_the_role_of_Th0_and_Th1_clones_in_autoimmune_thyroid_disease_by_use_of_Hu_SCID_chimeras_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090122997944317 DB - PRIME DP - Unbound Medicine ER -