Regional variation of the alphabeta T cell repertoire in the colon of healthy individuals and patients with Crohn's disease.
Clonally expanded T cells might be involved in the pathogenesis of Crohn's disease (CD). To test the impact of CD on the regional distribution of expanded T cells, this study analyzed the T cell receptor beta (TCRB) repertoire within colonic biopsy specimens from 12 CD patients and 6 noninflammatory controls by TCR spectratyping. Migration characteristics of dominant CDR3 bands from different sites of the normal mucosa suggested focal, segmental, or ubiquitous spreading of individual expanded clones. Similar patterns were observed when inflamed and noninflamed areas of the colon of CD patients were compared, suggesting that regional expansion of T cells was more closely related to anatomic proximity than to local inflammatory activity. CDR3-sequence analysis of TCRBV12+ T cells, which were selectively expanded in the inflamed colon of 3 CD patients, failed to reveal a public CDR3 motif. Our data indicate the existence of distinct patterns of regional T cell expansions in the normal gut mucosa, which are not significantly disrupted by chronic intestinal inflammation. This does not exclude a pathogenic role of expanded T cells in CD through more subtle changes, but emphasizes the need to distinguish them from a discontinuous distribution of clonally expanded T cells in normal colon.
May
Ekkehard
E
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. ekkemay@altavista.net
Lambert
Carsten
C
Holtmeier
Wolfgang
W
Hennemann
Andreas
A
Zeitz
Martin
M
Duchmann
Rainer
R
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D003106:Colon / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D022801:Complementarity Determining Regions / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000276:immunology*; D017421:Sequence Analysis
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta