DISTINCT VASCULAR-LESIONS IN GIANT-CELL ARTERITIS SHARE IDENTICAL T-CELL CLONOTYPES

被引:164
作者
WEYAND, CM
SCHONBERGER, J
OPPITZ, U
HUNDER, NNH
HICOK, KC
GORONZY, JJ
机构
[1] Division of Rheumatology, Mayo Clinic and Foundation, Rochester, MN
关键词
D O I
10.1084/jem.179.3.951
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Giant cell arteritis (GCA) is a spontaneous vasculitic syndrome that specifically targets the walls of medium and large arteries. Vascular lesions are characterized by patchy granulomatous infiltrates composed of T cells, macrophages, histiocytes, and giant cells. To test the hypothesis that a locally residing antigen recruits T cells into the vessel walls, we have analyzed T cell receptor (TCR) molecules of tissue infiltrating T cells. A total of 638 CD4(+) T cell clones were isolated from temporal artery specimens of three patients with GCA. Analysis of TCR molecules for the usage of V beta 1-V beta 20 revealed that all TCR V beta elements were represented, demonstrating that interleukin 2 (IL-2)-responsive T cells infiltrating the tissue are highly diverse. To detect expanded T cell specificities, we made use of the patchy character of the inflammatory disease and compared the TCR repertoire of T cells established from independent vasculitic foci of the same artery. Sequence analysis of TCR V beta chains documented that individual TCR specificities were present in multiple copies, indicating clonal expansion. T cells with identical beta chains were isolated from distinct inflammatory foci of the same patient. These specificities represented only a small fraction of tissue-infiltrating T cells and involved the V beta 5.3 gene segment in the two patients sharing the HLA-DRB1*0401 allele. The third complementarity determining region of clonally expanded TCR beta chains was characterized by a cluster of negatively and positively charged residues, suggesting that the juxtaposed antigenic peptide is charged. The sharing of identical T cell specificities by distinct and independent regions of the granulomatous inflammation suggests that these T cells are disease relevant and that their repertoire is strongly restricted. These data suggest that an antigen residing in the arterial wall is recognized by a small fraction of CD4(+) T cells in the inflammatory process characteristic for GCA.
引用
收藏
页码:951 / 960
页数:10
相关论文
共 33 条
[21]  
LIE JT, 1990, ARTHRITIS RHEUM-US, V33, P1074
[22]   SELECTION FOR T-CELL RECEPTOR V-BETA-D-BETA-J-BETA GENE REARRANGEMENTS WITH SPECIFICITY FOR A MYELIN BASIC-PROTEIN PEPTIDE IN BRAIN-LESIONS OF MULTIPLE-SCLEROSIS [J].
OKSENBERG, JR ;
PANZARA, MA ;
BEGOVICH, AB ;
MITCHELL, D ;
ERLICH, HA ;
MURRAY, RS ;
SHIMONKEVITZ, R ;
SHERRITT, M ;
ROTHBARD, J ;
BERNARD, CCA ;
STEINMAN, L .
NATURE, 1993, 362 (6415) :68-70
[23]   EVIDENCE FOR THE EFFECTS OF A SUPERANTIGEN IN RHEUMATOID-ARTHRITIS [J].
PALIARD, X ;
WEST, SG ;
LAFFERTY, JA ;
CLEMENTS, JR ;
KAPPLER, JW ;
MARRACK, P ;
KOTZIN, BL .
SCIENCE, 1991, 253 (5017) :325-329
[24]   BIASED AMINO-ACID DISTRIBUTIONS IN REGIONS OF THE T-CELL RECEPTORS AND MHC MOLECULES POTENTIALLY INVOLVED IN THEIR ASSOCIATION [J].
PROCHNICKACHALUFOUR, A ;
CASANOVA, JL ;
AVRAMEAS, S ;
CLAVERIE, JM ;
KOURILSKY, P .
INTERNATIONAL IMMUNOLOGY, 1991, 3 (09) :853-864
[25]   ACCESS TO A MESSENGER-RNA SEQUENCE OR ITS PROTEIN PRODUCT IS NOT LIMITED BY TISSUE OR SPECIES SPECIFICITY [J].
SARKAR, G ;
SOMMER, SS .
SCIENCE, 1989, 244 (4902) :331-334
[27]   ACTIVATION-INDEPENDENT BINDING OF HUMAN-MEMORY T-CELLS TO ADHESION MOLECULE ELAM-1 [J].
SHIMIZU, Y ;
SHAW, S ;
GRABER, N ;
GOPAL, TV ;
HORGAN, KJ ;
VANSEVENTER, GA ;
NEWMAN, W .
NATURE, 1991, 349 (6312) :799-802
[28]   RESTRICTED EXPRESSION OF T-CELL RECEPTOR V-BETA-GENES BUT NOT V-ALPHA-GENES IN RHEUMATOID-ARTHRITIS [J].
SOTTINI, A ;
IMBERTI, L ;
GORLA, R ;
CATTANEO, R ;
PRIMI, D .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (02) :461-466
[29]  
WEYAND C, 1992, ARTHRITIS RHEUM, V35, pS49
[30]   THE HLA-DRB1 LOCUS AS A GENETIC COMPONENT IN GIANT-CELL ARTERITIS - MAPPING OF A DISEASE-LINKED SEQUENCE MOTIF TO THE ANTIGEN-BINDING SITE OF THE HLA-DR MOLECULE [J].
WEYAND, CM ;
HICOK, KC ;
HUNDER, GG ;
GORONZY, JJ .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (06) :2355-2361