Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes

doi:10.1084/jem.176.1.187

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Poussier, P.
	Articles by Julius, M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Poussier, P.
	Articles by Julius, M.


Social Bookmarking

	What's this?

ARTICLES

Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes

P Poussier, P Edouard, C Lee, M Binnie and M Julius
Department of Medicine, McGill University, Montreal, Quebec, Canada.

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR- alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus- independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Zhou, R., Wei, H., Sun, R., Tian, Z. (2007). Recognition of Double-Stranded RNA by TLR3 Induces Severe Small Intestinal Injury in Mice. J. Immunol. 178: 4548-4556 [Abstract] [Full Text]
Bernard, D., Six, A., Rigottier-Gois, L., Messiaen, S., Chilmonczyk, S., Quillet, E., Boudinot, P., Benmansour, A. (2006). Phenotypic and Functional Similarity of Gut Intraepithelial and Systemic T Cells in a Teleost Fish. J. Immunol. 176: 3942-3949 [Abstract] [Full Text]
Miura, N., Yamamoto, M., Fukutake, M., Ohtake, N., Iizuka, S., Ishige, A., Sasaki, H., Fukuda, K., Yamamoto, T., Hayakawa, S. (2005). Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments. Int Immunol 17: 513-522 [Abstract] [Full Text]
Poussier, P., Ning, T., Murphy, T., Dabrowski, D., Ramanathan, S. (2005). Impaired Post-Thymic Development of Regulatory CD4+25+ T Cells Contributes to Diabetes Pathogenesis in BB Rats. J. Immunol. 174: 4081-4089 [Abstract] [Full Text]
Williams, A. M., Bland, P. W., Phillips, A. C., Turner, S., Brooklyn, T., Shaya, G., Spicer, R. D., Probert, C. S. J. (2004). Intestinal {alpha}{beta} T Cells Differentiate and Rearrange Antigen Receptor Genes In Situ in the Human Infant. J. Immunol. 173: 7190-7199 [Abstract] [Full Text]
Hoffman-Goetz, L., Quadrilatero, J., Boudreau, J., Guan, J. (2004). Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise. J. Appl. Physiol. 96: 2073-2081 [Abstract] [Full Text]
Saurer, L., Seibold, I., Rihs, S., Vallan, C., Dumrese, T., Mueller, C. (2004). Virus-Induced Activation of Self-Specific TCR{alpha}{beta} CD8{alpha}{alpha} Intraepithelial Lymphocytes Does Not Abolish Their Self-Tolerance in the Intestine. J. Immunol. 172: 4176-4183 [Abstract] [Full Text]
Poussier, P., Ning, T., Banerjee, D., Julius, M. (2002). A Unique Subset of Self-specific Intraintestinal T Cells Maintains Gut Integrity. J. Exp. Med. 195: 1491-1497 [Abstract] [Full Text]
Lee, H.-o., Cooper, C. J., Choi, J.-h., Alnadjim, Z., Barrett, T. A. (2002). The State of CD4+ T Cell Activation Is a Major Factor for Determining the Kinetics and Location of T Cell Responses to Oral Antigen. J. Immunol. 168: 3833-3838 [Abstract] [Full Text]
Ramanathan, S., Marandi, L., Poussier, P. (2002). 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. J. Immunol. 168: 2182-2187 [Abstract] [Full Text]
Alpdogan, O., Schmaltz, C., Muriglan, S. J., Kappel, B. J., Perales, M.-A., Rotolo, J. A., Halm, J. A., Rich, B. E., van den Brink, M. R. M. (2001). Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease. Blood 98: 2256-2265 [Abstract] [Full Text]
Podd, B. S., Aberg, C., Kudla, K. L., Keene, L., Tobias, E., Camerini, V. (2001). MHC Class I Allele Dosage Alters CD8 Expression by Intestinal Intraepithelial Lymphocytes. J. Immunol. 167: 2561-2568 [Abstract] [Full Text]
Huleatt, J. W., Pilip, I., Kerksiek, K., Pamer, E. G. (2001). Intestinal and Splenic T Cell Responses to Enteric Listeria monocytogenes Infection: Distinct Repertoires of Responding CD8 T Lymphocytes. J. Immunol. 166: 4065-4073 [Abstract] [Full Text]
Pignata, C., Gaetaniello, L., Masci, A. M., Frank, J., Christiano, A., Matrecano, E., Racioppi, L. (2001). Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation. Blood 97: 880-885 [Abstract] [Full Text]
Das, G., Gould, D. S., Augustine, M. M., Fragoso, G., Sciutto, E., Stroynowski, I., Van Kaer, L., Schust, D. J., Ploegh, H., Janeway, C. A. Jr. (2000). Qa-2-dependent Selection of CD8{alpha}/{alpha} T Cell Receptor {alpha}/{beta}+ Cells in Murine Intestinal Intraepithelial Lymphocytes. J. Exp. Med. 192: 1521-1528 [Abstract] [Full Text]
Wilson, A., Ferrero, I., MacDonald, H. R., Radtke, F. (2000). Cutting Edge: An Essential Role for Notch-1 in the Development of Both Thymus-Independent and -Dependent T Cells in the Gut. J. Immunol. 165: 5397-5400 [Abstract] [Full Text]
Boileau, C., Houde, M., Dulude, G., Clegg, C. H., Perreault, C. (2000). Regulation of Extrathymic T Cell Development and Turnover by Oncostatin M. J. Immunol. 164: 5713-5720 [Abstract] [Full Text]
Laky, K., Lefrancois, L., Lingenheld, E. G., Ishikawa, H., Lewis, J. M., Olson, S., Suzuki, K., Tigelaar, R. E., Puddington, L. (2000). Enterocyte Expression of Interleukin 7 Induces Development of {gamma}{delta} T Cells and Peyer's Patches. J. Exp. Med. 191: 1569-1580 [Abstract] [Full Text]
Oida, T., Suzuki, K., Nanno, M., Kanamori, Y., Saito, H., Kubota, E., Kato, S., Itoh, M., Kaminogawa, S., Ishikawa, H. (2000). Role of Gut Cryptopatches in Early Extrathymic Maturation of Intestinal Intraepithelial T Cells. J. Immunol. 164: 3616-3626 [Abstract] [Full Text]
Ito, K., Takaishi, H., Jin, Y., Song, F., Denning, T. L., Ernst, P. B. (2000). Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10. J. Immunol. 164: 2994-3001 [Abstract] [Full Text]
Matsuda, J. L., Gapin, L., Sydora, B. C., Byrne, F., Binder, S., Kronenberg, M., Aranda, R. (2000). Systemic Activation and Antigen-Driven Oligoclonal Expansion of T Cells in a Mouse Model of Colitis. J. Immunol. 164: 2797-2806 [Abstract] [Full Text]
Muller, S., Buhler-Jungo, M., Mueller, C. (2000). Intestinal Intraepithelial Lymphocytes Exert Potent Protective Cytotoxic Activity During an Acute Virus Infection. J. Immunol. 164: 1986-1994 [Abstract] [Full Text]
Marguerat, S., MacDonald, H. R., Kraehenbuhl, J.-P., van Meerwijk, J. P. M. (1999). Protection from Radiation-Induced Colitis Requires MHC Class II Antigen Expression by Cells of Hemopoietic Origin. J. Immunol. 163: 4033-4040 [Abstract] [Full Text]
Das, G., Janeway, C. A. , Jr. (1999). Development of CD8{alpha}/{alpha} and CD8{alpha}/{beta} T Cells in Major Histocompatibility Complex Class I�deficient Mice. J. Exp. Med. 190: 881-884 [Abstract] [Full Text]
Adjei, A. A., Jones, J. T., Riggs, M. W., Enriquez, F. J. (1999). Evidence of Thymus-Independent Local and Systemic Antibody Responses to Cryptosporidium parvum Infection in Nude Mice. Infect. Immun. 67: 3947-3951 [Abstract] [Full Text]
Saparov, A., Kraus, L. A., Cong, Y., Marwill, J., Xu, X.-Y., Elson, C. O., Weaver, C. T. (1999). Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR. Int Immunol 11: 1253-1264 [Abstract] [Full Text]
Kohyama, M., Nanno, M., Kawaguchi-Miyashita, M., Shimada, S., Watanabe, M., Hibi, T., Kaminogawa, S., Ishikawa, H. (1999). Cytolytic and IFN-gamma -producing activities of gamma delta T cells in the mouse intestinal epithelium are T cell receptor-beta -chain dependent. Proc. Natl. Acad. Sci. USA 96: 7451-7455 [Abstract] [Full Text]
Helgeland, L., Johansen, F.-E., Utgaard, J. O., Vaage, J. T., Brandtzaeg, P. (1999). Oligoclonality of Rat Intestinal Intraepithelial T Lymphocytes: Overlapping TCR {beta}-Chain Repertoires in the CD4 Single-Positive and CD4/CD8 Double-Positive Subsets. J. Immunol. 162: 2683-2692 [Abstract] [Full Text]
Page, S. T., Bogatzki, L. Y., Hamerman, J. A., Malissen, M., Perlmutter, R. M., Pullen, A. M. (1999). Differential effects of manipulating signaling in early T cell development in intestinal intraepithelial lymphocytes and thymocytes. Int Immunol 11: 169-177 [Abstract] [Full Text]
Howie, D., Spencer, J., DeLord, D., Pitzalis, C., Wathen, N. C., Dogan, A., Akbar, A., MacDonald, T. T. (1998). Extrathymic T Cell Differentiation in the Human Intestine Early in Life. J. Immunol. 161: 5862-5872 [Abstract] [Full Text]
Shaw, S. K., Hermanowski-Vosatka, A., Shibahara, T., McCormick, B. A., Parkos, C. A., Carlson, S. L., Ebert, E. C., Brenner, M. B., Madara, J. L. (1998). Migration of intestinal intraepithelial lymphocytes into a polarized epithelial monolayer. Am. J. Physiol. Gastrointest. Liver Physiol. 275: G584-G591 [Abstract] [Full Text]
Yamada, H., Ninomiya, T., Hashimoto, A., Tamada, K., Takimoto, H., Nomoto, K. (1998). Positive Selection of Extrathymically Developed T Cells by Self-antigens. J. Exp. Med. 188: 779-784 [Abstract] [Full Text]
Page, S. T., Bogatzki, L. Y., Hamerman, J. A., Sweenie, C. H., Hogarth, P. J., Malissen, M., Perlmutter, R. M., Pullen, A. M. (1998). Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor alpha beta lineage. Proc. Natl. Acad. Sci. USA 95: 9459-9464 [Abstract] [Full Text]
Cruz, D., Sydora, B. C., Hetzel, K., Yakoub, G., Kronenberg, M., Cheroutre, H. (1998). An Opposite Pattern of Selection of a Single T Cell Antigen Receptor in the Thymus and among Intraepithelial Lymphocytes. J. Exp. Med. 188: 255-265 [Abstract] [Full Text]
Laky, K., Lefrancois, L., von Freeden-Jeffry, U., Murray, R., Puddington, L. (1998). The Role of IL-7 in Thymic and Extrathymic Development of TCR{gamma}{delta} Cells. J. Immunol. 161: 707-713 [Abstract] [Full Text]
Ramanathan, S., Norwich, K., Poussier, P. (1998). Antigen Activation Rescues Recent Thymic Emigrants from Programmed Cell Death in the BB Rat. J. Immunol. 160: 5757-5764 [Abstract] [Full Text]
McVay, L. D., Jaswal, S. S., Kennedy, C., Hayday, A., Carding, S. R. (1998). The Generation of Human {gamma}{delta} T Cell Repertoires During Fetal Development. J. Immunol. 160: 5851-5860 [Abstract] [Full Text]
Guehler, S. R., Finch, R. J., Bluestone, J. A., Barrett, T. A. (1998). Increased Threshold for TCR-Mediated Signaling Controls Self Reactivity of Intraepithelial Lymphocytes. J. Immunol. 160: 5341-5346 [Abstract] [Full Text]
Saito, H., Kanamori, Y., Takemori, T., Nariuchi, H., Kubota, E., Takahashi-Iwanaga, H., Iwanaga, T., Ishikawa, H. (1998). Generation of Intestinal T Cells from Progenitors Residing in Gut Cryptopatches. Science 280: 275-278 [Abstract] [Full Text]
Camerini, V., Sydora23, B. C., Aranda, R., Nguyen, C., MacLean, C., McBride, W. H., Kronenberg, M. (1998). Generation of Intestinal Mucosal Lymphocytes in SCID Mice Reconstituted with Mature, Thymus-Derived T Cells. J. Immunol. 160: 2608-2618 [Abstract] [Full Text]
McCarthy, S. A., Mainwaring, M. S., Dougall, D. S., Lamouse-Smith, E. S. (1998). Activation Requirements, Lytic Mechanism, and Development of a Novel Anti-CD8-Resistant CTL Population. J. Immunol. 160: 2715-2724 [Abstract] [Full Text]
Hurst, S. D., Sitterding, S. M., Ji, S., Barrett, T. A. (1997). Functional differentiation of T cells in the intestine of T cell receptor�transgenic�mice. Proc. Natl. Acad. Sci. USA 94: 3920-3925 [Abstract] [Full Text]
Wang, J, Klein, JR (1994). Thymus-neuroendocrine interactions in extrathymic T cell development. Science 265: 1860-1862 [Abstract]
Penninger, J, Kishihara, K, Molina, T, Wallace, V., Timms, E, Hedrick, S., Mak, T. (1993). Requirement for tyrosine kinase p56lck for thymic development of transgenic gamma delta T cells. Science 260: 358-361 [Abstract]