Abstract
We have reassessed the possible role of the adhesion molecule ICAM-1 in the pathogenesis of thyroid autoimmunity. In order to do that, we have investigated its expression in eight Graves' thyroids both in vivo (i.e. on cryostat sections and on cell suspensions), and in vitro (i.e. on cells cultured in monolayers for 3 days), and the results were compared with those obtained with similar preparations from four normal glands. On cryostat sections, the expression of ICAM-1, and for comparison that of HLA Class I and Class II molecules, was studied by immunofluorescence (IFL), but the former were also assessed by a distinct immunohistochemical technique. ICAM-1 was not detected in thyrocytes in vivo of both normal and Graves' glands, but solely in endothelial cells and antigen-presenting cells (APC). This selective reaction was confirmed by a four-layer technique using specific markers which identify endothelial cells and thyrocytes. HLA Class II molecules were confirmed to be inappropriately expressed in thyrocytes of Graves' glands, but there was no co-expression of these products and ICAM-1 in the same cells. In contrast, ICAM-1 appeared de novo in a proportion of Graves' and normal thyrocytes soon after the attachment and spreading of these cells in monolayer cultures (36-48 h). Graves' thyrocytes showed a quantitatively higher degree of expression compared with that detected on normal thyroid cells (40-70% versus 12-20%). Under these experimental conditions, the four-layer staining with thyroid microsomal antibodies confirmed that thyrocytes were indeed the positive cells which expressed ICAM-1. Blocking experiments with cultured thyrocytes from two Graves' glands and MoAbs to tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) did not prevent the occurrence of ICAM-1 expression. As a result of our study, we failed to demonstrate that Graves' thyrocytes express ICAM-1 in vivo. The unexpected case of inducing ICAM-1 on thyroid cells under certain in vitro conditions remains intriguing. The phenomenon could be the simple consequence of a mechanical effect rather than exerted by specific biological processes. Further investigations are, therefore, needed to establish whether ICAM-1 is really involved in the pathogenesis of Graves' disease.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Altmann D. M., Hogg N., Trowsdale J., Wilkinson D. Cotransfection of ICAM-1 and HLA-DR reconstitutes human antigen-presenting cell function in mouse L cells. Nature. 1989 Apr 6;338(6215):512–514. doi: 10.1038/338512a0. [DOI] [PubMed] [Google Scholar]
- Bagnasco M., Caretto A., Olive D., Pedini B., Canonica G. W., Betterle C. Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer. Clin Exp Immunol. 1991 Feb;83(2):309–313. doi: 10.1111/j.1365-2249.1991.tb05633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell I. L., Cutri A., Wilkinson D., Boyd A. W., Harrison L. C. Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4282–4286. doi: 10.1073/pnas.86.11.4282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Annu Rev Immunol. 1991;9:27–66. doi: 10.1146/annurev.iy.09.040191.000331. [DOI] [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
- Dustin M. L., Staunton D. E., Springer T. A. Supergene families meet in the immune system. Immunol Today. 1988 Jul-Aug;9(7-8):213–215. doi: 10.1016/0167-5699(88)91216-9. [DOI] [PubMed] [Google Scholar]
- Frohman M., Francfort J. W., Cowing C. T-dependent destruction of thyroid isografts exposed to IFN-gamma. J Immunol. 1991 Apr 1;146(7):2227–2234. [PubMed] [Google Scholar]
- Grubeck-Loebenstein B., Buchan G., Chantry D., Kassal H., Londei M., Pirich K., Barrett K., Turner M., Waldhausl W., Feldmann M. Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. Clin Exp Immunol. 1989 Sep;77(3):324–330. [PMC free article] [PubMed] [Google Scholar]
- Hanafusa T., Pujol-Borrell R., Chiovato L., Doniach D., Bottazzo G. F. In vitro and in vivo reversal of thyroid epithelial polarity: its relevance for autoimmune thyroid disease. Clin Exp Immunol. 1984 Sep;57(3):639–646. [PMC free article] [PubMed] [Google Scholar]
- Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R. C., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet. 1983 Nov 12;2(8359):1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
- Kennedy R. L., Jones T. H. Cytokines in endocrinology: their roles in health and in disease. J Endocrinol. 1991 May;129(2):167–178. doi: 10.1677/joe.0.1290167. [DOI] [PubMed] [Google Scholar]
- Londei M., Bottazzo G. F., Feldmann M. Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science. 1985 Apr 5;228(4695):85–89. doi: 10.1126/science.3871967. [DOI] [PubMed] [Google Scholar]
- MacKenzie W. A., Schwartz A. E., Friedman E. W., Davies T. F. Intrathyroidal T cell clones from patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 1987 Apr;64(4):818–824. doi: 10.1210/jcem-64-4-818. [DOI] [PubMed] [Google Scholar]
- Makgoba M. W., Sanders M. E., Ginther Luce G. E., Gugel E. A., Dustin M. L., Springer T. A., Shaw S. Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol. 1988 Apr;18(4):637–640. doi: 10.1002/eji.1830180423. [DOI] [PubMed] [Google Scholar]
- Makgoba M. W., Sanders M. E., Shaw S. The CD2-LFA-3 and LFA-1-ICAM pathways: relevance to T-cell recognition. Immunol Today. 1989 Dec;10(12):417–422. doi: 10.1016/0167-5699(89)90039-X. [DOI] [PubMed] [Google Scholar]
- Marlin S. D., Springer T. A. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987 Dec 4;51(5):813–819. doi: 10.1016/0092-8674(87)90104-8. [DOI] [PubMed] [Google Scholar]
- Martin A., Huber G. K., Davies T. F. Induction of human thyroid cell ICAM-1 (CD54) antigen expression and ICAM-1-mediated lymphocyte binding. Endocrinology. 1990 Aug;127(2):651–657. doi: 10.1210/endo-127-2-651. [DOI] [PubMed] [Google Scholar]
- Miyazaki A., Hanafusa T., Itoh N., Miyagawa J., Kono N., Tarui S., Kiyotaki C., Yoshizaki K. Demonstration of interleukin-1 beta on perifollicular endothelial cells in the thyroid glands of patients with Graves' disease. J Clin Endocrinol Metab. 1989 Oct;69(4):738–744. doi: 10.1210/jcem-69-4-738. [DOI] [PubMed] [Google Scholar]
- Miyazaki A., Mirakian R., Bottazzo G. F. Adhesion molecule expression in Graves' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes. Clin Exp Immunol. 1992 Jul;89(1):52–57. doi: 10.1111/j.1365-2249.1992.tb06876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parham P. Intolerable secretion in tolerant transgenic mice. Nature. 1988 Jun 9;333(6173):500–503. doi: 10.1038/333500a0. [DOI] [PubMed] [Google Scholar]
- Pujol-Borrell R., Bottazzo G. F. Puzzling diabetic transgenic mice: a lesson for human type 1 diabetes? Immunol Today. 1988 Oct;9(10):303–306. doi: 10.1016/0167-5699(88)91322-9. [DOI] [PubMed] [Google Scholar]
- Pujol-Borrell R., Hanafusa T., Chiovato L., Bottazzo G. F. Lectin-induced expression of DR antigen on human cultured follicular thyroid cells. Nature. 1983 Jul 7;304(5921):71–73. doi: 10.1038/304071a0. [DOI] [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
- Staunton D. E., Marlin S. D., Stratowa C., Dustin M. L., Springer T. A. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988 Mar 25;52(6):925–933. doi: 10.1016/0092-8674(88)90434-5. [DOI] [PubMed] [Google Scholar]
- Stockinger B., Pessara U., Lin R. H., Habicht J., Grez M., Koch N. A role of Ia-associated invariant chains in antigen processing and presentation. Cell. 1989 Feb 24;56(4):683–689. doi: 10.1016/0092-8674(89)90590-4. [DOI] [PubMed] [Google Scholar]
- Todd I., Pujol-Borrell R., Abdul-Karim B. A., Hammond L. J., Feldmann M., Bottazzo G. F. HLA-D subregion expression by thyroid epithelium in autoimmune thyroid diseases and induced in vitro. Clin Exp Immunol. 1987 Sep;69(3):532–542. [PMC free article] [PubMed] [Google Scholar]
- Tolosa E., Roura C., Catálfamo M., Martí M., Lucas-Martín A., Sanmartí A., Salinas I., Obiols G., Foz-Sala M., Pujol-Borrell R. Expression of intercellular adhesion molecule-1 in thyroid follicular cells in autoimmune, non-autoimmune and neoplastic diseases of the thyroid gland: discordance with HLA. J Autoimmun. 1992 Feb;5(1):107–118. doi: 10.1016/s0896-8411(05)80055-1. [DOI] [PubMed] [Google Scholar]
- Tolosa E., Roura C., Martí M., Belfiore A., Pujol-Borrell R. Induction of intercellular adhesion molecule-1 but not of lymphocyte function-associated antigen-3 in thyroid follicular cells. J Autoimmun. 1992 Feb;5(1):119–135. doi: 10.1016/s0896-8411(05)80056-3. [DOI] [PubMed] [Google Scholar]
- Vives M., Soldevila G., Alcalde L., Lorenzo C., Somoza N., Pujol-Borrell R. Adhesion molecules in human islet beta-cells. De novo induction of ICAM-1 but not LFA-3. Diabetes. 1991 Nov;40(11):1382–1390. doi: 10.2337/diab.40.11.1382. [DOI] [PubMed] [Google Scholar]
- Weetman A. P., Cohen S., Makgoba M. W., Borysiewicz L. K. Expression of an intercellular adhesion molecule, ICAM-1, by human thyroid cells. J Endocrinol. 1989 Jul;122(1):185–191. doi: 10.1677/joe.0.1220185. [DOI] [PubMed] [Google Scholar]
- Weetman A. P., Volkman D. J., Burman K. D., Margolick J. B., Petrick P., Weintraub B. D., Fauci A. S. The production and characterization of thyroid-derived T-cell lines in Graves' disease and Hashimoto's thyroiditis. Clin Immunol Immunopathol. 1986 Apr;39(1):139–150. doi: 10.1016/0090-1229(86)90213-8. [DOI] [PubMed] [Google Scholar]
- Zheng R. Q., Abney E. R., Chu C. Q., Field M., Maini R. N., Lamb J. R., Feldmann M. Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells. Immunology. 1992 Mar;75(3):456–462. [PMC free article] [PubMed] [Google Scholar]
- Zheng R. Q., Abney E. R., Grubeck-Loebenstein B., Dayan C., Maini R. N., Feldmann M. Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 on human thyroid epithelial cells in Graves' and Hashimoto's diseases. J Autoimmun. 1990 Dec;3(6):727–736. doi: 10.1016/s0896-8411(05)80039-3. [DOI] [PubMed] [Google Scholar]
- Zoppi G., Gasparini R., Mantovanelli F., Gobio-Casali L., Astolfi R., Crovari P. Diet and antibody response to vaccinations in healthy infants. Lancet. 1983 Jul 2;2(8340):11–14. doi: 10.1016/s0140-6736(83)90004-1. [DOI] [PubMed] [Google Scholar]



