Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 July 2004:
Vol. 305. no. 5681, pp. 248 - 251
DOI: 10.1126/science.1096472
Prev | Table of Contents | Next

Reports

Thymic Origin of Intestinal {alpha}ß T Cells Revealed by Fate Mapping of ROR{gamma}t+ Cells

Gérard Eberl1*{dagger} and Dan R. Littman1,2{dagger}

Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in host mucosal immunity and, unlike other T cells, have been proposed to differentiate from local precursors rather than from thymocytes. We show here that IELs expressingthe {alpha}ß T cell receptor are derived from precursors that express ROR{gamma}t, an orphan nuclear hormone receptor detected only in immature CD4+CD8+ thymocytes, fetal lymphoid tissue–inducer (LTi) cells, and LTi-like cells in cryptopatches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal {alpha}ß T cells are progeny of CD4+CD8+ thymocytes, indicatingthat the adult intestine is not a significant site for {alpha}ß T cell development. Our results suggest that intestinal ROR{gamma}t+ cells are local organizers of mucosal lymphoid tissue.

1 Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
2 Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.



* Present address: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.

{dagger} To whom correspondence should be addressed. E-mail: geberl{at}adarc.org (G.E.); littman{at}saturn.med.nyu.edu (D.R.L.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Trans-Presentation of IL-15 by Intestinal Epithelial Cells Drives Development of CD8{alpha}{alpha} IELs.
L. J. Ma, L. F. Acero, T. Zal, and K. S. Schluns (2009)
J. Immunol. 183, 1044-1054
   Abstract »    Full Text »    PDF »
Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor ROR{gamma}t.
M. Ayyoub, F. Deknuydt, I. Raimbaud, C. Dousset, L. Leveque, G. Bioley, and D. Valmori (2009)
PNAS 106, 8635-8640
   Abstract »    Full Text »    PDF »
Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells.
A. Awasthi, L. Riol-Blanco, A. Jager, T. Korn, C. Pot, G. Galileos, E. Bettelli, V. K. Kuchroo, and M. Oukka (2009)
J. Immunol. 182, 5904-5908
   Abstract »    Full Text »    PDF »
Uneven Colonization of the Lymphoid Periphery by T Cells That Undergo Early TCR{alpha} Rearrangements.
D. W. Hendricks and P. J. Fink (2009)
J. Immunol. 182, 4267-4274
   Abstract »    Full Text »    PDF »
Chemokine Receptor CXCR5 Supports Solitary Intestinal Lymphoid Tissue Formation, B Cell Homing, and Induction of Intestinal IgA Responses.
S. Velaga, H. Herbrand, M. Friedrichsen, T. Jiong, M. Dorsch, M. W. Hoffmann, R. Forster, and O. Pabst (2009)
J. Immunol. 182, 2610-2619
   Abstract »    Full Text »    PDF »
Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?.
A Bas, G Forsberg, V Sjoberg, S Hammarstrom, O Hernell, and M-L Hammarstrom (2009)
Gut 58, 189-195
   Abstract »    Full Text »    PDF »
Identification of CD25+ {gamma}{delta} T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers.
K. Shibata, H. Yamada, R. Nakamura, X. Sun, M. Itsumi, and Y. Yoshikai (2008)
J. Immunol. 181, 5940-5947
   Abstract »    Full Text »    PDF »
In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ ROR{gamma}t+ T cells.
M. Lochner, L. Peduto, M. Cherrier, S. Sawa, F. Langa, R. Varona, D. Riethmacher, M. Si-Tahar, J. P. Di Santo, and G. Eberl (2008)
J. Exp. Med. 205, 1381-1393
   Abstract »    Full Text »    PDF »
T cell receptor-instructed {alpha}{beta} versus {gamma}{delta} lineage commitment revealed by single-cell analysis.
T. Kreslavsky, A. I. Garbe, A. Krueger, and H. von Boehmer (2008)
J. Exp. Med. 205, 1173-1186
   Abstract »    Full Text »    PDF »
IL-15 Does Not Affect IEL Development in the Thymus but Regulates Homeostasis of Putative Precursors and Mature CD8{alpha}{alpha}+ IELs in the Intestine.
Y.-G. Lai, M.-S. Hou, Y.-W. Hsu, C.-L. Chang, Y.-H. Liou, M.-H. Tsai, F. Lee, and N.-S. Liao (2008)
J. Immunol. 180, 3757-3765
   Abstract »    Full Text »    PDF »
Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions.
J. H. Niess, F. Leithauser, G. Adler, and J. Reimann (2008)
J. Immunol. 180, 559-568
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium.
J. Kunisawa, Y. Kurashima, M. Higuchi, M. Gohda, I. Ishikawa, I. Ogahara, N. Kim, M. Shimizu, and H. Kiyono (2007)
J. Exp. Med. 204, 2335-2348
   Abstract »    Full Text »    PDF »
Multiple Constraints at the Level of TCR{alpha} Rearrangement Impact V{alpha}14i NKT Cell Development.
E. Hager, A. Hawwari, J. L. Matsuda, M. S. Krangel, and L. Gapin (2007)
J. Immunol. 179, 2228-2234
   Abstract »    Full Text »    PDF »
Lymphotoxin-Independent Expression of TNF-Related Activation-Induced Cytokine by Stromal Cells in Cryptopatches, Isolated Lymphoid Follicles, and Peyer's Patches.
R. T. Taylor, S. R. Patel, E. Lin, B. R. Butler, J. G. Lake, R. D. Newberry, and I. R. Williams (2007)
J. Immunol. 178, 5659-5667
   Abstract »    Full Text »    PDF »
The same genomic region conditions clonal deletion and clonal deviation to the CD8{alpha}{alpha} and regulatory T cell lineages in NOD versus C57BL/6 mice.
P. D. Holler, T. Yamagata, W. Jiang, M. Feuerer, C. Benoist, and D. Mathis (2007)
PNAS 104, 7187-7192
   Abstract »    Full Text »    PDF »
Mouse TCR{alpha}beta+CD8{alpha}{alpha} Intraepithelial Lymphocytes Express Genes That Down-Regulate Their Antigen Reactivity and Suppress Immune Responses.
T. L. Denning, S. Granger, D. Mucida, R. Graddy, G. Leclercq, W. Zhang, K. Honey, J. P. Rasmussen, H. Cheroutre, A. Y. Rudensky, et al. (2007)
J. Immunol. 178, 4230-4239
   Abstract »    Full Text »    PDF »
CC Chemokine Receptor 6 Expression by B Lymphocytes Is Essential for the Development of Isolated Lymphoid Follicles.
K. G. McDonald, J. S. McDonough, C. Wang, T. Kucharzik, I. R. Williams, and R. D. Newberry (2007)
Am. J. Pathol. 170, 1229-1240
   Abstract »    Full Text »    PDF »
Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease.
K. Lahl, C. Loddenkemper, C. Drouin, J. Freyer, J. Arnason, G. Eberl, A. Hamann, H. Wagner, J. Huehn, and T. Sparwasser (2007)
J. Exp. Med. 204, 57-63
   Abstract »    Full Text »    PDF »
Adaptation of Solitary Intestinal Lymphoid Tissue in Response to Microbiota and Chemokine Receptor CCR7 Signaling.
O. Pabst, H. Herbrand, M. Friedrichsen, S. Velaga, M. Dorsch, G. Berhardt, T. Worbs, A. J. Macpherson, and R. Forster (2006)
J. Immunol. 177, 6824-6832
   Abstract »    Full Text »    PDF »
Neonatal and Adult CD4+CD3- Cells Share Similar Gene Expression Profile, and Neonatal Cells Up-Regulate OX40 Ligand in Response to TL1A (TNFSF15)..
M.-Y. Kim, K.-M. Toellner, A. White, F. M. McConnell, F. M. C. Gaspal, S. M. Parnell, E. Jenkinson, G. Anderson, and P. J. L. Lane (2006)
J. Immunol. 177, 3074-3081
   Abstract »    Full Text »    PDF »
Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue.
M. F. Cesta (2006)
Toxicol Pathol 34, 599-608
   Abstract »    Full Text »    PDF »
T Cells in Cryptopatch Aggregates Share TCR {gamma} Variable Region Junctional Sequences with {gamma}{delta} T Cells in the Small Intestinal Epithelium of Mice..
B. S. Podd, J. Thoits, N. Whitley, H.-Y. Cheng, K. L. Kudla, H. Taniguchi, J. Halkias, K. Goth, and V. Camerini (2006)
J. Immunol. 176, 6532-6542
   Abstract »    Full Text »    PDF »
TCR{gamma}{delta} Intraepithelial Lymphocytes Are Required for Self-Tolerance..
N. R. Locke, S. Stankovic, D. P. Funda, and L. C. Harrison (2006)
J. Immunol. 176, 6553-6559
   Abstract »    Full Text »    PDF »
Detection and Characterization of Hemopoietic Stem Cells in the Adult Human Small Intestine.
L. Lynch, D. O'Donoghue, J. Dean, J. O'Sullivan, C. O'Farrelly, and L. Golden-Mason (2006)
J. Immunol. 176, 5199-5204
   Abstract »    Full Text »    PDF »
ROR{gamma}t Recruits Steroid Receptor Coactivators to Ensure Thymocyte Survival.
H. Xie, M. S. Sadim, and Z. Sun (2005)
J. Immunol. 175, 3800-3809
   Abstract »    Full Text »    PDF »
The timing of TCR{alpha} expression critically influences T cell development and selection.
T. A. Baldwin, M. M. Sandau, S. C. Jameson, and K. A. Hogquist (2005)
J. Exp. Med. 202, 111-121
   Abstract »    Full Text »    PDF »
Comment on "Thymic Origin of Intestinal {alpha}{beta} T Cells Revealed by Fate Mapping of ROR{gamma}t+ Cells".
B. Rocha (2005)
Science 308, 1553a
   Full Text »    PDF »
Response to Comment on "Thymic Origin of Intestinal {alpha}{beta} T Cells Revealed by Fate Mapping of ROR{gamma}t+ Cells".
G. Eberl and D. R Littman (2005)
Science 308, 1553b
   Full Text »    PDF »
Adaptive Immune Responses Are Dispensable for Isolated Lymphoid Follicle Formation: Antigen-Naive, Lymphotoxin-Sufficient B Lymphocytes Drive the Formation of Mature Isolated Lymphoid Follicles.
K. G. McDonald, J. S. McDonough, and R. D. Newberry (2005)
J. Immunol. 174, 5720-5728
   Abstract »    Full Text »    PDF »
Two distinctive pathways for recruitment of naive and primed IgM+ B cells to the gut lamina propria.
K. Suzuki, B. Meek, Y. Doi, T. Honjo, and S. Fagarasan (2005)
PNAS 102, 2482-2486
   Abstract »    Full Text »    PDF »
Intestinal {gamma}{delta} T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer's Patches, and Isolated Lymphoid Follicles.
S. Nonaka, T. Naito, H. Chen, M. Yamamoto, K. Moro, H. Kiyono, H. Hamada, and H. Ishikawa (2005)
J. Immunol. 174, 1906-1912
   Abstract »    Full Text »    PDF »
Intestinal Cryptopatch Formation in Mice Requires Lymphotoxin {alpha} and the Lymphotoxin {beta} Receptor.
R. T. Taylor, A. Lugering, K. A. Newell, and I. R. Williams (2004)
J. Immunol. 173, 7183-7189
   Abstract »    Full Text »    PDF »
The Fourth Way? Harnessing Aggressive Tendencies in the Thymus.
T. A. Baldwin, K. A. Hogquist, and S. C. Jameson (2004)
J. Immunol. 173, 6515-6520
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)