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 10 April 1998:
Vol. 280. no. 5361, pp. 275 - 278
DOI: 10.1126/science.280.5361.275
Prev | Table of Contents | Next

Reports

Generation of Intestinal T Cells from Progenitors Residing in Gut Cryptopatches

Hisashi Saito, Yutaka Kanamori, Toshitada Takemori, Hideo Nariuchi, Eiro Kubota, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga, Hiromichi Ishikawa *

Cryptopatches (CPs) are part of the murine intestinal immune compartment. Cells isolated from CPs of the small intestine that were c-kit positive (c-kit+) but lineage markers negative (Lin-) gave rise to T cell receptor (TCR) alpha beta and TCR gamma delta intestinal intraepithelial T cells after in vivo transfer or tissue engraftment into severe combined immunodeficient mice. In contrast, cells from Peyer's patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit+Lin- cells, failed to do so. These findings and results of electron microscopic analysis provide evidence of a local intestinal T cell precursor that develops in the CPs.

H. Saito, Y. Kanamori, H. Ishikawa, Department of Microbiology, Keio University School of Medicine, Tokyo 160, Japan.
T. Takemori, Department of Immunology, National Institute of Infectious Diseases, Tokyo 162, Japan.
H. Nariuchi, Department of Allergology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan.
E. Kubota, Second Department of Oral and Maxillofacial Surgery, Kanagawa Dental College, Kanagawa 238, Japan.
H. Takahashi-Iwanaga, Department of Anatomy, School of Medicine, Hokkaido University, Sapporo 060, Japan.
T. Iwanaga, Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060, Japan.
*   To whom correspondence should be addressed. E-mail: ishikawa{at}sun.microb.med.keio.ac.jp

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 »
Intestinal double-positive CD4+CD8+ T cells of neonatal rhesus macaques are proliferating, activated memory cells and primary targets for SIVMAC251 infection.
X. Wang, A. Das, A. A. Lackner, R. S. Veazey, and B. Pahar (2008)
Blood 112, 4981-4990
   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 »
Stimulatory and costimulatory effects of IL-18 directed to different small intestinal CD43 T cell subsets.
D. Montufar-Solis, H.-C. Wang, and J. R. Klein (2007)
J. Leukoc. Biol. 82, 1166-1173
   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 »
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 »
Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue.
M. F. Cesta (2006)
Toxicol Pathol 34, 599-608
   Abstract »    Full Text »    PDF »
A ticket to the gut for thymic T cells.
W Falk (2006)
Gut 55, 910-912
   Full Text »    PDF »
Foxp3-Expressing CD103+ Regulatory T Cells Accumulate in Dendritic Cell Aggregates of the Colonic Mucosa in Murine Transfer Colitis.
F. Leithauser, T. Meinhardt-Krajina, K. Fink, B. Wotschke, P. Moller, and J. Reimann (2006)
Am. J. Pathol. 168, 1898-1909
   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 »
The immune system as a regulator of thyroid hormone activity..
J. R. Klein (2006)
Experimental Biology and Medicine 231, 229-236
   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 »
Phenotypic Characterization of CD3-7+ Cells in Developing Human Intestine and an Analysis of Their Ability to Differentiate into T Cells.
U. Gunther, J. A. Holloway, J. G. Gordon, A. Knight, V. Chance, N. A. Hanley, D. I. Wilson, R. French, J. Spencer, H. Steer, et al. (2005)
J. Immunol. 174, 5414-5422
   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 »
Improved thymic function in exclusively breastfed infants is associated with higher interleukin 7 concentrations in their mothers' breast milk.
P. T Ngom, A. C Collinson, J. Pido-Lopez, S. M Henson, A. M Prentice, and R. Aspinall (2004)
Am. J. Clinical Nutrition 80, 722-728
   Abstract »    Full Text »    PDF »
Thymic Origin of Intestinal {alpha}{beta} T Cells Revealed by Fate Mapping of ROR{gamma}t+ Cells.
G. Eberl and D. R. Littman (2004)
Science 305, 248-251
   Abstract »    Full Text »    PDF »
Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor {alpha} expression.
K. S. Schluns, E. C. Nowak, A. Cabrera-Hernandez, L. Puddington, L. Lefrancois, and H. L. Aguila (2004)
PNAS 101, 5616-5621
   Abstract »    Full Text »    PDF »
Lung Cells Transplanted to Irradiated Recipients Generate Lymphohematopoietic Progeny.
S. Abe, G. Lauby, C. Boyer, L. Manouilova, S. I. Rennard, and J. G. Sharp (2004)
Am. J. Respir. Cell Mol. Biol. 30, 491-499
   Abstract »    Full Text »    PDF »
Modulating the intestinal immune system: the role of lymphotoxin and GALT organs.
T W Spahn and T Kucharzik (2004)
Gut 53, 456-465
   Full Text »    PDF »
Influence of the Route of Infection on Development of T-Cell Receptor {beta}-Chain Repertoires of Reovirus-Specific Cytotoxic T Lymphocytes.
J. R. Fulton, J. Smith, C. Cunningham, and C. F. Cuff (2004)
J. Virol. 78, 1582-1590
   Abstract »    Full Text »    PDF »
Functionally active CD8{alpha}{beta}+ TCR{gamma}{delta} intestinal intraepithelial lymphocytes in athymic nu/nu mice.
Y. Emoto, M. Emoto, M. Miyamoto, I. Yoshizawa, and S. H. E. Kaufmann (2004)
Int. Immunol. 16, 111-117
   Abstract »    Full Text »    PDF »
T Cell Receptor Revision Does Not Solely Target Recent Thymic Emigrants.
C. J. Cooper, M. T. Orr, C. J. McMahan, and P. J. Fink (2003)
J. Immunol. 171, 226-233
   Abstract »    Full Text »    PDF »
Expression of recombination-activating gene in mature peripheral T cells in Peyer's patch.
E. Kondo, H. Wakao, H. Koseki, T. Takemori, S. Kojo, M. Harada, M. Takahashi, S. Sakata, C. Shimizu, T. Ito, et al. (2003)
Int. Immunol. 15, 393-402
   Abstract »    Full Text »    PDF »
Extrathymic T Cell Lymphopoiesis: Ontogeny and Contribution to Gut Intraepithelial Lymphocytes in Athymic and Euthymic Mice.
D. Guy-Grand, O. Azogui, S. Celli, S. Darche, M. C. Nussenzweig, P. Kourilsky, and P. Vassalli (2003)
J. Exp. Med. 197, 333-341
   Abstract »    Full Text »    PDF »
Serial Analysis of Gene Expression in Circulating {gamma}{delta} T Cell Subsets Defines Distinct Immunoregulatory Phenotypes and Unexpected Gene Expression Profiles.
N. Meissner, J. Radke, J. F. Hedges, M. White, M. Behnke, S. Bertolino, M. Abrahamsen, and M. A. Jutila (2003)
J. Immunol. 170, 356-364
   Abstract »    Full Text »    PDF »
Pivotal role of CCL25 (TECK)-CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes.
N. Onai, M. Kitabatake, Y.-y. Zhang, H. Ishikawa, S. Ishikawa, and K. Matsushima (2002)
Int. Immunol. 14, 687-694
   Abstract »    Full Text »    PDF »
CD8{alpha}-Deficient Mice Are Highly Susceptible to 5-Fluorouracil-Induced Lethality.
N. Itoh, H. Nishimura, T. Matsuguchi, T. Yajima, Y. Mokuno, T. Hiromatsu, Y. Nimura, and Y. Yoshikai (2002)
Clin. Vaccine Immunol. 9, 550-557
   Abstract »    Full Text »    PDF »
Evidence for the Extrathymic Origin of Intestinal TCR{gamma}{delta}+ T Cells in Normal Rats and for an Impairment of This Differentiation Pathway in BB Rats.
S. Ramanathan, L. Marandi, and P. Poussier (2002)
J. Immunol. 168, 2182-2187
   Abstract »    Full Text »    PDF »
Characterization of T Cell Differentiation in the Murine Gut.
F. Lambolez, O. Azogui, A.-M. Joret, C. Garcia, H. von Boehmer, J. Di Santo, S. Ezine, and B. Rocha (2002)
J. Exp. Med. 195, 437-449
   Abstract »    Full Text »    PDF »
Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver.
I. Douagi, F. Colucci, J. P. Di Santo, and A. Cumano (2002)
Blood 99, 463-471
   Abstract »    Full Text »    PDF »
Contributions from Self-Renewal and Trafficking to the Uterine NK Cell Population of Early Pregnancy.
S. Chantakru, C. Miller, L. E. Roach, W. A. Kuziel, N. Maeda, W.-C. Wang, S. S. Evans, and B. A. Croy (2002)
J. Immunol. 168, 22-28
   Abstract »    Full Text »    PDF »
Identification of Multiple Isolated Lymphoid Follicles on the Antimesenteric Wall of the Mouse Small Intestine.
H. Hamada, T. Hiroi, Y. Nishiyama, H. Takahashi, Y. Masunaga, S. Hachimura, S. Kaminogawa, H. Takahashi-Iwanaga, T. Iwanaga, H. Kiyono, et al. (2002)
J. Immunol. 168, 57-64
   Abstract »    Full Text »    PDF »
In situ demonstration of intraepithelial lymphocyte adhesion to villus microvessels of the small intestine.
S. Koseki, S. Miura, H. Fujimori, R. Hokari, S. Komoto, Y. Hara, T. Ogino, H. Nagata, M. Goto, S. Hachimura, et al. (2001)
Int. Immunol. 13, 1165-1174
   Abstract »    Full Text »    PDF »
Differential Roles of Cytokine Receptors in the Development of Epidermal {gamma}{delta} T Cells.
S.-K. Ye, K. Maki, H.-C. Lee, A. Ito, K. Kawai, H. Suzuki, T. W. Mak, Y.-h. Chien, T. Honjo, and K. Ikuta (2001)
J. Immunol. 167, 1929-1934
   Abstract »    Full Text »    PDF »
Development of Intestinal Intraepithelial Lymphocytes, NK Cells, and NK 1.1+ T Cells in CD45-Deficient Mice.
S. M. Martin, I. K. Mehta, W. M. Yokoyama, M. L. Thomas, and R. G. Lorenz (2001)
J. Immunol. 166, 6066-6073
   Abstract »    Full Text »    PDF »
Lymphocyte Lineages at Mucosal Effector Sites: Rat Salivary Glands.
N. L. O'Sullivan, C. A. Skandera, and P. C. Montgomery (2001)
J. Immunol. 166, 5522-5529
   Abstract »    Full Text »    PDF »
Comparison of Gastritis and Gastric Epithelial Proliferation in Helicobacter heilmannii-infected Nude and BALB/c Mice.
R. A. Peterson, S. J. Danon, and K. A. Eaton (2001)
Vet. Pathol. 38, 173-183
   Abstract »    Full Text »    PDF »
Probiotics: effects on immunity.
E. Isolauri, Y. Sutas, P. Kankaanpaa, H. Arvilommi, and S. Salminen (2001)
Am. J. Clinical Nutrition 73, 444S-450
   Abstract »    Full Text »    PDF »
Qa-2-dependent Selection of CD8{alpha}/{alpha} T Cell Receptor {alpha}/{beta}+ Cells in Murine Intestinal Intraepithelial Lymphocytes.
G. Das, D. S. Gould, M. M. Augustine, G. Fragoso, E. Sciutto, I. Stroynowski, L. Van Kaer, D. J. Schust, H. Ploegh, and C. A. Janeway Jr. (2000)
J. Exp. Med. 192, 1521-1528
   Abstract »    Full Text »    PDF »
Cutting Edge: An Essential Role for Notch-1 in the Development of Both Thymus-Independent and -Dependent T Cells in the Gut.
A. Wilson, I. Ferrero, H. R. MacDonald, and F. Radtke (2000)
J. Immunol. 165, 5397-5400
   Abstract »    Full Text »    PDF »
IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses.
T. Hiroi, M. Yanagita, N. Ohta, G. Sakaue, and H. Kiyono (2000)
J. Immunol. 165, 4329-4337
   Abstract »    Full Text »    PDF »
The Ins and Outs of Body Surface Immunology.
A. Hayday and J. L. Viney (2000)
Science 290, 97-100
   Abstract »    Full Text »
A Primitive T Cell-Independent Mechanism of Intestinal Mucosal IgA Responses to Commensal Bacteria.
A. J. Macpherson, D. Gatto, E. Sainsbury, G. R. Harriman, H. Hengartner, and R. M. Zinkernagel (2000)
Science 288, 2222-2226
   Abstract »    Full Text »
Regulation of Extrathymic T Cell Development and Turnover by Oncostatin M.
C. Boileau, M. Houde, G. Dulude, C. H. Clegg, and C. Perreault (2000)
J. Immunol. 164, 5713-5720
   Abstract »    Full Text »    PDF »
Stable and functional lymphoid reconstitution of common cytokine receptor gamma chain deficient mice by retroviral-mediated gene transfer.
C. Soudais, T. Shiho, L. I. Sharara, D. Guy-Grand, T. Taniguchi, A. Fischer, and J. P. Di Santo (2000)
Blood 95, 3071-3077
   Abstract »    Full Text »    PDF »
Enterocyte Expression of Interleukin 7 Induces Development of {gamma}{delta} T Cells and Peyer's Patches.
K. Laky, L. Lefrancois, E. G. Lingenheld, H. Ishikawa, J. M. Lewis, S. Olson, K. Suzuki, R. E. Tigelaar, and L. Puddington (2000)
J. Exp. Med. 191, 1569-1580
   Abstract »    Full Text »    PDF »
Human Bronchial Intraepithelial T Lymphocytes as a Distinct T-Cell Subset . Their Long-Term Survival in SCID-Hu Chimeras.
E. Goto, H. Kohrogi, N. Hirata, K. Tsumori, S. Hirosako, J. Hamamoto, K. Fujii, O. Kawano, and M. Ando (2000)
Am. J. Respir. Cell Mol. Biol. 22, 405-411
   Abstract »    Full Text »
Role of Gut Cryptopatches in Early Extrathymic Maturation of Intestinal Intraepithelial T Cells.
T. Oida, K. Suzuki, M. Nanno, Y. Kanamori, H. Saito, E. Kubota, S. Kato, M. Itoh, S. Kaminogawa, and H. Ishikawa (2000)
J. Immunol. 164, 3616-3626
   Abstract »    Full Text »    PDF »
Differential Contribution of Fas- and Perforin-Mediated Mechanisms to the Cell-Mediated Cytotoxic Activity of Naive and In Vivo-Primed Intestinal Intraepithelial Lymphocytes.
N. Corazza, S. Muller, T. Brunner, D. Kagi, and C. Mueller (2000)
J. Immunol. 164, 398-403
   Abstract »    Full Text »    PDF »
Differential expression of CD43 isoforms on murine T cells and their relationship to acute intestinal graft versus host disease: studies using enhanced-green fluorescent protein transgenic mice.
E. U. Bagriacik, M. D. Armstrong, M. Okabe, and J. R. Klein (1999)
Int. Immunol. 11, 1651-1662
   Abstract »    Full Text »    PDF »
Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR.
A. Saparov, L. A. Kraus, Y. Cong, J. Marwill, X.-Y. Xu, C. O. Elson, and C. T. Weaver (1999)
Int. Immunol. 11, 1253-1264
   Abstract »    Full Text »    PDF »
Massive Activation-Induced Cell Death of Alloreactive T Cells With Apoptosis of Bystander Postthymic T Cells Prevents Immune Reconstitution in Mice With Graft-Versus-Host Disease.
S. Brochu, B. Rioux-Masse, J. Roy, D.-C. Roy, and C. Perreault (1999)
Blood 94, 390-400
   Abstract »    Full Text »    PDF »
Differential Roles of Segmented Filamentous Bacteria and Clostridia in Development of the Intestinal Immune System.
Y. Umesaki, H. Setoyama, S. Matsumoto, A. Imaoka, and K. Itoh (1999)
Infect. Immun. 67, 3504-3511
   Abstract »    Full Text »    PDF »
Cytolytic and IFN-gamma -producing activities of gamma delta T cells in the mouse intestinal epithelium are T cell receptor-beta -chain dependent.
M. Kohyama, M. Nanno, M. Kawaguchi-Miyashita, S. Shimada, M. Watanabe, T. Hibi, S. Kaminogawa, and H. Ishikawa (1999)
PNAS 96, 7451-7455
   Abstract »    Full Text »    PDF »
High- and low-affinity single-peptide/MHC ligands have distinct effects on the development of mucosal CD8alpha alpha and CD8alpha beta T lymphocytes.
C. N. Levelt, Y. P. de Jong, E. Mizoguchi, C. O'Farrelly, A. K. Bhan, S. Tonegawa, C. Terhorst, and S. J. Simpson (1999)
PNAS 96, 5628-5633
   Abstract »    Full Text »    PDF »
Gastrointestinal Epithelium Is an Early Extrathymic Site for Increased Prevalence of CD34+ Progenitor Cells in Contrast to the Thymus during Primary Simian Immunodeficiency Virus Infection.
J. J. Mattapallil, Z. Smit-McBride, and S. Dandekar (1999)
J. Virol. 73, 4518-4523
   Abstract »    Full Text »
The Effect of Graft-versus-Host Disease on T Cell Production and Homeostasis.
G. Dulude, D.-C. Roy, and C. Perreault (1999)
J. Exp. Med. 189, 1329-1342
   Abstract »    Full Text »    PDF »
Differential effects of manipulating signaling in early T cell development in intestinal intraepithelial lymphocytes and thymocytes.
S. T. Page, L. Y. Bogatzki, J. A. Hamerman, M. Malissen, R. M. Perlmutter, and A. M. Pullen (1999)
Int. Immunol. 11, 169-177
   Abstract »    Full Text »    PDF »
Extrathymic T Cell Differentiation in the Human Intestine Early in Life.
D. Howie, J. Spencer, D. DeLord, C. Pitzalis, N. C. Wathen, A. Dogan, A. Akbar, and T. T. MacDonald (1998)
J. Immunol. 161, 5862-5872
   Abstract »    Full Text »    PDF »
Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor alpha beta lineage.
S. T. Page, L. Y. Bogatzki, J. A. Hamerman, C. H. Sweenie, P. J. Hogarth, M. Malissen, R. M. Perlmutter, and A. M. Pullen (1998)
PNAS 95, 9459-9464
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

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