Abstract
To study the possible role of T cells bearing the gamma delta T cell receptor (TCR) heterodimer in the pathogenesis of autoimmune chronic active hepatitis (AI-CAH) and primary sclerosing cholangitis (PSC) in children, we measured levels of gamma delta+ T cells in the peripheral blood, assessed the proportion of cells bearing the disulphide-linked (BB3+) and non-disulphide-linked (A13+) subtypes of the receptor, and studied the co-expression of TCR-gamma delta and the activation markers HLA-DR and IL-2 receptor (IL-2R), and the memory cell marker CD45RO. Percentage levels and absolute numbers of gamma delta +T cells were higher in both groups of patients than in controls (P less than 0.01), mainly as a result of an increase in both percentage levels and absolute numbers of the A13+ subtype (P less than 0.001). Co-expression of IL-2R and TCR-gamma delta was not found in controls but was present in some patients with AI-CAH (four out of 17) and PSC (six out of 12) at low levels (median 2.3%, range 1.7-5.0%). Expression of HLA-DR on gamma delta+ T cells was similar in both groups of patients and controls. The majority of gamma delta+ T cells in children with AI-CAH and PSC also expressed CD45RO (74.7 +/- 18.4% and 79.8 +/- 24.3%, respectively) at levels significantly higher than in controls (53.3 +/- 17.2%, P less than 0.01). These results suggest that autoimmune liver diseases in children are associated with an expansion and activation of gamma delta+ T cells in the peripheral blood, which may be important in the pathogenesis of these disorders.
Full text
PDF![78](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df04/1554410/682a678b370a/clinexpimmunol00045-0080.png)
![79](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df04/1554410/80067c608404/clinexpimmunol00045-0081.png)
![80](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df04/1554410/f642d9a7caaf/clinexpimmunol00045-0082.png)
![81](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df04/1554410/50565fe61aa4/clinexpimmunol00045-0083.png)
![82](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df04/1554410/85c2b44377fa/clinexpimmunol00045-0084.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Austen K. F. Opening remarks for the Elmer Becker Symposium. Clin Immunol Immunopathol. 1989 Jan;50(1 Pt 1):5–7. doi: 10.1016/0090-1229(89)90216-x. [DOI] [PubMed] [Google Scholar]
- Autran B., Triebel F., Katlama C., Rozenbaum W., Hercend T., Debre P. T cell receptor gamma/delta+ lymphocyte subsets during HIV infection. Clin Exp Immunol. 1989 Feb;75(2):206–210. [PMC free article] [PubMed] [Google Scholar]
- Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
- Borst J., van Dongen J. J., Bolhuis R. L., Peters P. J., Hafler D. A., de Vries E., van de Griend R. J. Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody. J Exp Med. 1988 May 1;167(5):1625–1644. doi: 10.1084/jem.167.5.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bottino C., Tambussi G., Ferrini S., Ciccone E., Varese P., Mingari M. C., Moretta L., Moretta A. Two subsets of human T lymphocytes expressing gamma/delta antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor. J Exp Med. 1988 Aug 1;168(2):491–505. doi: 10.1084/jem.168.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carding S. R., McNamara J. G., Pan M., Bottomly K. Characterization of gamma/delta T cell clones isolated from human fetal liver and thymus. Eur J Immunol. 1990 Jun;20(6):1327–1335. doi: 10.1002/eji.1830200619. [DOI] [PubMed] [Google Scholar]
- Feldmann M., Londei M., Grubeck-Loebenstein B., De Berardinis P., Leech Z., Turner M., Barrett K., Buchan G., Maini R. N. Understanding what infiltrating cells do in autoimmunity: combination of cellular and molecular approaches. Transplant Proc. 1988 Apr;20(2):311–314. [PubMed] [Google Scholar]
- Ferrini S., Prigione I., Bottino C., Ciccone E., Tambussi G., Mammoliti S., Moretta L., Moretta A. Monoclonal antibodies which react with the T cell receptor gamma/delta recognize different subsets of CD3+WT31- T lymphocytes. Eur J Immunol. 1989 Jan;19(1):57–61. doi: 10.1002/eji.1830190110. [DOI] [PubMed] [Google Scholar]
- Halstensen T. S., Scott H., Brandtzaeg P. Intraepithelial T cells of the TcR gamma/delta+ CD8- and V delta 1/J delta 1+ phenotypes are increased in coeliac disease. Scand J Immunol. 1989 Dec;30(6):665–672. doi: 10.1111/j.1365-3083.1989.tb02474.x. [DOI] [PubMed] [Google Scholar]
- Hedlund G., Sandberg-Wollheim M., Sjögren H. O. Increased proportion of CD4+CDw29+CD45R-UCHL-1+ lymphocytes in the cerebrospinal fluid of both multiple sclerosis patients and healthy individuals. Cell Immunol. 1989 Feb;118(2):406–412. doi: 10.1016/0008-8749(89)90388-2. [DOI] [PubMed] [Google Scholar]
- Jensen D. M., McFarlane I. G., Portmann B. S., Eddleston A. L., Williams R. Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis. N Engl J Med. 1978 Jul 6;299(1):1–7. doi: 10.1056/NEJM197807062990101. [DOI] [PubMed] [Google Scholar]
- Keystone E. C., Rittershaus C., Wood N., Snow K. M., Flatow J., Purvis J. C., Poplonski L., Kung P. C. Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 1991 Apr;84(1):78–82. [PMC free article] [PubMed] [Google Scholar]
- Kjeldsen-Kragh J., Quayle A., Kalvenes C., Førre O., Sørskaar D., Vinje O., Thoen J., Natvig J. B. T gamma delta cells in juvenile rheumatoid arthritis and rheumatoid arthritis. In the juvenile rheumatoid arthritis synovium the T gamma delta cells express activation antigens and are predominantly V delta 1+, and a significant proportion of these patients have elevated percentages of T gamma delta cells. Scand J Immunol. 1990 Dec;32(6):651–659. doi: 10.1111/j.1365-3083.1990.tb03207.x. [DOI] [PubMed] [Google Scholar]
- Kontiainen S., Toomath R., Lowder J., Feldmann M. Selective activation of T cells in newly diagnosed insulin-dependent diabetic patients: evidence for heterogeneity of T cell receptor usage. Clin Exp Immunol. 1991 Mar;83(3):347–351. doi: 10.1111/j.1365-2249.1991.tb05641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lobo-Yeo A., Alviggi L., Mieli-Vergani G., Portmann B., Mowat A. P., Vergani D. Preferential activation of helper/inducer T lymphocytes in autoimmune chronic active hepatitis. Clin Exp Immunol. 1987 Jan;67(1):95–104. [PMC free article] [PubMed] [Google Scholar]
- McFarlane B. M., McSorley C. G., Vergani D., McFarlane I. G., Williams R. Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. J Hepatol. 1986;3(2):196–205. doi: 10.1016/s0168-8278(86)80026-5. [DOI] [PubMed] [Google Scholar]
- Morio T., Nagasawa M., Nonoyama S., Okawa H., Yata J. Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome. J Immunol. 1990 Feb 15;144(4):1270–1275. [PubMed] [Google Scholar]
- Ohteki T., Abo T., Seki S., Kobata T., Yagita H., Okumura K., Kumagai K. Predominant appearance of gamma/delta T lymphocytes in the liver of mice after birth. Eur J Immunol. 1991 Jul;21(7):1733–1740. doi: 10.1002/eji.1830210722. [DOI] [PubMed] [Google Scholar]
- Selmaj K., Brosnan C. F., Raine C. S. Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6452–6456. doi: 10.1073/pnas.88.15.6452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith M. D., Bröker B., Moretta L., Ciccone E., Grossi C. E., Edwards J. C., Yüksel F., Colaco B., Worman C., Mackenzie L. T gamma delta cells and their subsets in blood and synovial tissue from rheumatoid arthritis patients. Scand J Immunol. 1990 Dec;32(6):585–593. doi: 10.1111/j.1365-3083.1990.tb03200.x. [DOI] [PubMed] [Google Scholar]
- Sturm E., Braakman E., Bontrop R. E., Chuchana P., Van de Griend R. J., Koning F., Lefranc M. P., Bolhuis R. L. Coordinated V gamma and V delta gene segment rearrangements in human T cell receptor gamma/delta+ lymphocytes. Eur J Immunol. 1989 Jul;19(7):1261–1265. doi: 10.1002/eji.1830190717. [DOI] [PubMed] [Google Scholar]
- Viney J., MacDonald T. T., Spencer J. Gamma/delta T cells in the gut epithelium. Gut. 1990 Aug;31(8):841–844. doi: 10.1136/gut.31.8.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wen L., Peakman M., Lobo-Yeo A., McFarlane B. M., Mowat A. P., Mieli-Vergani G., Vergani D. T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis. Lancet. 1990 Dec 22;336(8730):1527–1530. doi: 10.1016/0140-6736(90)93306-a. [DOI] [PubMed] [Google Scholar]
- el-Shabrawi M., Wilkinson M. L., Portmann B., Mieli-Vergani G., Chong S. K., Williams R., Mowat A. P. Primary sclerosing cholangitis in childhood. Gastroenterology. 1987 May;92(5 Pt 1):1226–1235. doi: 10.1016/s0016-5085(87)91082-1. [DOI] [PubMed] [Google Scholar]