The Journal of Immunology, Vol 158, Issue 12 5632-5641, Copyright © 1997 by American Association of Immunologists

ARTICLES

The TCR-delta repertoire in human intestine undergoes characteristic changes during fetal to adult development

W Holtmeier, T Witthoft, A Hennemann, HS Winter and MF Kagnoff
Department of Medicine, University of California, San Diego, La Jolla 92093, USA.

The TCR-delta repertoire in adult human intestine is oligoclonal and unique in each individual. In the present study, changes in the junctional regions of TCR-delta transcripts in human intestine that occur during development from fetal to adult life were used to characterize fundamental changes in the TCR-delta repertoire in the human intestinal tract during ontogeny. At mid-gestation, the fetal repertoire was polyclonal, but limited, in its junctional diversity by the relative lack of N region nucleotide additions and by the frequent formation of coding region joins at regions of short sequence homology. In addition, identical TCRDV2 transcripts that resemble canonical TCR- delta sequences in mice were present in the intestine of different fetuses. In the early period after birth, the intestinal TCR-delta repertoire was polyclonal, and more diverse than the fetal repertoire, with junctional regions that contained extensive N nucleotide additions and frequently were as complex as those of adults. The intestinal TCR- delta repertoire showed increasing restriction with age and, by 14 to 17 yr, the repertoire was oligoclonal and resembled the repertoire of individuals in the sixth to seventh decade. Moreover, the adult TCR- delta repertoire was almost identical at multiple sites throughout the intestine, suggesting a model in which gammadelta T cell clones, selected by ligands in the intestinal tract, undergo expansion and recirculation before lodging throughout the small intestine or colon.

This article has been cited by other articles:

				I. Van Rhijn, V. P. M. G. Rutten, B. Charleston, M. Smits, W. van Eden, and A. P. Koets Massive, sustained {gamma}{delta} T cell migration from the bovine skin in vivo J. Leukoc. Biol., April 1, 2007; 81(4): 968 - 973. [Abstract] [Full Text] [PDF]

				A. M. Williams, P. W. Bland, A. C. Phillips, S. Turner, T. Brooklyn, G. Shaya, R. D. Spicer, and C. S. J. Probert Intestinal {alpha}{beta} T Cells Differentiate and Rearrange Antigen Receptor Genes In Situ in the Human Infant J. Immunol., December 15, 2004; 173(12): 7190 - 7199. [Abstract] [Full Text] [PDF]

				J. Lee, K. Choi, M. R. Olin, S.-N. Cho, and T. W. Molitor {gamma}{delta} T Cells in Immunity Induced by Mycobacterium bovis Bacillus Calmette-Guerin Vaccination Infect. Immun., March 1, 2004; 72(3): 1504 - 1511. [Abstract] [Full Text] [PDF]

				A. Bas, S. G. Hammarstrom, and M.-L. K. C. Hammarstrom Extrathymic TCR Gene Rearrangement in Human Small Intestine: Identification of New Splice Forms of Recombination Activating Gene-1 mRNA with Selective Tissue Expression J. Immunol., October 1, 2003; 171(7): 3359 - 3371. [Abstract] [Full Text] [PDF]

				W. Holtmeier, J. Kaller, W. Geisel, R. Pabst, W. F. Caspary, and H. J. Rothkotter Development and Compartmentalization of the Porcine TCR {delta} Repertoire at Mucosal and Extraintestinal Sites: The Pig as a Model for Analyzing the Effects of Age and Microbial Factors J. Immunol., August 15, 2002; 169(4): 1993 - 2002. [Abstract] [Full Text] [PDF]

				W. Holtmeier, A. Hennemann, E. May, R. Duchmann, and W. F. Caspary T cell receptor delta repertoire in inflamed and noninflamed colon of patients with IBD analyzed by CDR3 spectratyping Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1024 - G1034. [Abstract] [Full Text] [PDF]

				A. V. MacDougall, P. Enders, G. Hatfield, D. C. Pauza, and E. Rakasz V{{gamma}}2 TCR Repertoire Overlap in Different Anatomical Compartments of Healthy, Unrelated Rhesus Macaques J. Immunol., February 15, 2001; 166(4): 2296 - 2302. [Abstract] [Full Text] [PDF]

				T. Kubota, J.-y. Wang, T. W. F. Gobel, R. D. Hockett, M. D. Cooper, and C.-l. H. Chen Characterization of an Avian (Gallus gallus domesticus) TCR {alpha}{delta} Gene Locus J. Immunol., October 1, 1999; 163(7): 3858 - 3866. [Abstract] [Full Text] [PDF]

				A. Steinle, V. Groh, and T. Spies Diversification, expression, and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules PNAS, October 13, 1998; 95(21): 12510 - 12515. [Abstract] [Full Text] [PDF]

				L. D. McVay, S. S. Jaswal, C. Kennedy, A. Hayday, and S. R. Carding The Generation of Human {gamma}{delta} T Cell Repertoires During Fetal Development J. Immunol., June 15, 1998; 160(12): 5851 - 5860. [Abstract] [Full Text] [PDF]

				V. Groh, A. Steinle, S. Bauer, and T. Spies Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial T Cells Science, March 13, 1998; 279(5357): 1737 - 1740. [Abstract] [Full Text]

				M. F. Kagnoff III. Ontogeny and function of gamma delta T cells in the intestine Am J Physiol Gastrointest Liver Physiol, March 1, 1998; 274(3): G455 - G458. [Abstract] [Full Text] [PDF]