Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function

doi:10.1084/jem.170.5.1569

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Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function

T Goodman and L Lefrancois
Department of Cell Biology, Upjohn Company, Kalamazoo, Michigan 49001.

The function and structure of the TCR proteins of intraepithelial lymphocytes (IEL) were examined using a panel of mAbs specific for TCR- gamma/delta. Three subsets of TCR-gamma/delta+ IEL could be detected with five mAbs, termed GL1-GL5. The mAbs were able to trigger lysis via crosslinking of the IEL TCR and all of the subsets were constitutively cytolytic. Immunoprecipitation of IEL TCR proteins revealed that the GL2 mAb reacted only with gamma, delta heterodimers containing high Mr delta chains, while the other mAbs precipitated all of the observed gamma and delta proteins. Two-color fluorescence analysis showed that the GL2+ subset was contained within the larger GL1+ subset. The GL3 and GL4 mAbs appear to be specific for all TCR-gamma/delta while GL2 was V delta 4 specific. Analysis of IEL for TCR-alpha/beta expression demonstrated that approximately 20% of B6 IEL were TCR-alpha/beta+. Interestingly, this population of IEL contained Thy-1- and CT1+ cells, indicating that the unique phenotype of IEL was not restricted to TCR- gamma/delta+ cells. Moreover, the TCR-alpha/beta+ IEL were also constitutively cytolytic, suggesting that the intestinal milieu was controlling the functional programming of IEL regardless of TCR type. The mAbs reported here as well as the ability to exploit the distinct phenotype of IEL should prove useful in determining the function of IEL and the TCR-gamma/delta.
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Lugering, A., Kucharzik, T., Soler, D., Picarella, D., Hudson, J. T. III, Williams, I. R. (2003). Lymphoid Precursors in Intestinal Cryptopatches Express CCR6 and Undergo Dysregulated Development in the Absence of CCR6. J. Immunol. 171: 2208-2215 [Abstract] [Full Text]
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Kanehiro, A., Lahn, M., Makela, M. J., Dakhama, A., Joetham, A., Rha, Y.-H., Born, W., Gelfand, E. W. (2002). Requirement for the p75 TNF-{alpha} Receptor 2 in the Regulation of Airway Hyperresponsiveness by {gamma}{delta} T Cells. J. Immunol. 169: 4190-4197 [Abstract] [Full Text]
Lahn, M., Kanehiro, A., Takeda, K., Terry, J., Hahn, Y.-S., Aydintug, M. K., Konowal, A., Ikuta, K., O'Brien, R. L., Gelfand, E. W., Born, W. K. (2002). MHC class I-dependent Vgamma 4+ pulmonary T cells regulate alpha beta T cell-independent airway responsiveness. Proc. Natl. Acad. Sci. USA 99: 8850-8855 [Abstract] [Full Text]
Uehara, S., Grinberg, A., Farber, J. M., Love, P. E. (2002). A Role for CCR9 in T Lymphocyte Development and Migration. J. Immunol. 168: 2811-2819 [Abstract] [Full Text]
KANEHIRO, A., LAHN, M., MAKELA, M. J., DAKHAMA, A., FUJITA, M., JOETHAM, A., MASON, R. J., BORN, W., GELFAND, E. W. (2001). Tumor Necrosis Factor-alpha Negatively Regulates Airway Hyperresponsiveness through gamma delta T Cells. Am. J. Respir. Crit. Care Med. 164: 2229-2238 [Abstract] [Full Text]
Wang, H.-C., Klein, J. R. (2001). Multiple Levels of Activation of Murine CD8+ Intraepithelial Lymphocytes Defined by OX40 (CD134) Expression: Effects on Cell-Mediated Cytotoxicity, IFN-{gamma}, and IL-10 Regulation. J. Immunol. 167: 6717-6723 [Abstract] [Full Text]
Lefrancois, L., Vezys, V. (2001). Transgenic Mouse Model of Intestine-Specific Mucosal Injury and Repair. J Natl Cancer Inst Monogr 2001: 21-25 [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]
Skelsey, M. E., Mellon, J., Niederkorn, J. Y. (2001). {{gamma}}{{delta}}T Cells Are Needed for Ocular Immune Privilege and Corneal Graft Survival. J. Immunol. 166: 4327-4333 [Abstract] [Full Text]
Pope, C., Kim, S.-K., Marzo, A., Williams, K., Jiang, J., Shen, H., Lefrancois, L. (2001). Organ-Specific Regulation of the CD8 T Cell Response to Listeria monocytogenes Infection. J. Immunol. 166: 3402-3409 [Abstract] [Full Text]
Masopust, D., Jiang, J., Shen, H., Lefrancois, L. (2001). Direct Analysis of the Dynamics of the Intestinal Mucosa CD8 T Cell Response to Systemic Virus Infection. J. Immunol. 166: 2348-2356 [Abstract] [Full Text]
Berger, M. A., Carleton, M., Rhodes, M., Sauder, J. M., Trop, S., Dunbrack, R. L., Hugo, P., Wiest, D. L. (2000). Identification of a novel pre-TCR isoform in which the accessibility of the TCR{beta} subunit is determined by occupancy of the `missing' V domain of pre-T{alpha}. Int Immunol 12: 1579-1591 [Abstract] [Full Text]
Cady, C. T., Lahn, M., Vollmer, M., Tsuji, M., Seo, S. J., Reardon, C. L., O'Brien, R. L., Born, W. K. (2000). Response of Murine {gamma}{delta} T Cells to the Synthetic Polypeptide Poly-Glu50Tyr50 1. J. Immunol. 165: 1790-1798 [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. JEM 191: 1569-1580 [Abstract] [Full Text]
Müller–Röver, S., Bulfone–Paus, S., Handjiski, B., Welker, P., Sundberg, J. P., McKay, I. A., Botchkarev, V. A., Paus, R. (2000). Intercellular Adhesion Molecule-1 and Hair Follicle Regression. J. Histochem. Cytochem. 48: 557-568 [Abstract] [Full Text]
Schramm, C. M., Puddington, L., Yiamouyiannis, C. A., Lingenheld, E. G., Whiteley, H. E., Wolyniec, W. W., Noonan, T. C., Thrall, R. S. (2000). Proinflammatory Roles of T-Cell Receptor (TCR)gamma delta and TCRalpha beta Lymphocytes in a Murine Model of Asthma. Am. J. Respir. Cell Mol. Bio. 22: 218-225 [Abstract] [Full Text]
Lai, Y.-G., Gelfanov, V., Gelfanova, V., Kulik, L., Chu, C.-L., Jeng, S.-W., Liao, N.-S. (1999). IL-15 Promotes Survival But Not Effector Function Differentiation of CD8+ TCR{alpha}{beta}+ Intestinal Intraepithelial Lymphocytes. J. Immunol. 163: 5843-5850 [Abstract] [Full Text]
Kim, S.-K., Schluns, K. S., Lefrancois, L. (1999). Induction and Visualization of Mucosal Memory CD8 T Cells Following Systemic Virus Infection. J. Immunol. 163: 4125-4132 [Abstract] [Full Text]
Wilson, A., Capone, M., MacDonald, H. R. (1999). Unexpectedly late expression of intracellular CD3{epsilon} and TCR {gamma}{delta} proteins during adult thymus development. Int Immunol 11: 1641-1650 [Abstract] [Full Text]
Hayashi, R. J., Kanagawa, O. (1999). Unique CD4+ T cells in TCR {alpha} chain-deficient class I MHC-restricted TCR transgenic mice: role in a superantigen-mediated disease process. Int Immunol 11: 1581-1590 [Abstract] [Full Text]
Yiamouyiannis, C. A., Schramm, C. M., Puddington, L., Stengel, P., Baradaran-Hosseini, E., Wolyniec, W. W., Whiteley, H. E., Thrall, R. S. (1999). Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model. Am. J. Pathol. 154: 1911-1921 [Abstract] [Full Text]
Lefrancois, L., Parker, C. M., Olson, S., Muller, W., Wagner, N., Puddington, L. (1999). The Role of {beta}7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response. JEM 189: 1631-1638 [Abstract] [Full Text]
Cebra, J. J (1999). Influences of microbiota on intestinal immune system development. Am. J. Clin. Nutr. 69 : 1046S-1051S [Abstract] [Full Text]
Mukasa, A., Born, W. K., O'Brien, R. L. (1999). Inflammation Alone Evokes the Response of a TCR-Invariant Mouse {gamma}{delta} T Cell Subset. J. Immunol. 162: 4910-4913 [Abstract] [Full Text]
Seixas, E. M. G., Langhorne, J. (1999). {gamma}{delta}T Cells Contribute to Control of Chronic Parasitemia in Plasmodium chabaudi Infections in Mice. J. Immunol. 162: 2837-2841 [Abstract] [Full Text]
Chu, C.-L., Chen, S.-S., Wu, T.-S., Kuo, S.-C., Liao, N.-S. (1999). Differential Effects of IL-2 and IL-15 on the Death and Survival of Activated TCR{gamma}{delta}+ Intestinal Intraepithelial Lymphocytes. J. Immunol. 162: 1896-1903 [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]
Eynon, E. E., Livak, F., Kuida, K., Schatz, D. G., Flavell, R. A. (1999). Distinct Effects of Jak3 Signaling on {alpha}{beta} and {gamma}{delta} Thymocyte Development. J. Immunol. 162: 1448-1459 [Abstract] [Full Text]
Kim, S.-K., Reed, D. S., Olson, S., Schnell, M. J., Rose, J. K., Morton, P. A., Lefrancois, L. (1998). Generation of mucosal cytotoxic T cells against soluble protein by tissue-specific environmental and costimulatory signals. Proc. Natl. Acad. Sci. USA 95: 10814-10819 [Abstract] [Full Text]
Rajan, A. J., Klein, J. D. S., Brosnan, C. F. (1998). The Effect of {gamma}{delta} T Cell Depletion on Cytokine Gene Expression in Experimental Allergic Encephalomyelitis. J. Immunol. 160: 5955-5962 [Abstract] [Full Text]
Lahn, M., Kalataradi, H., Mittelstadt, P., Pflum, E., Vollmer, M., Cady, C., Mukasa, A., Vella, A. T., Ikle, D., Harbeck, R., O'Brien, R., Born, W. (1998). Early Preferential Stimulation of {gamma}{delta} T Cells by TNF-{alpha}. J. Immunol. 160: 5221-5230 [Abstract] [Full Text]
Kusunoki, Y., Chen, W., Martin, P. J. (1998). Prevention of Marrow Graft Rejection Without Induction of Graft-Versus-Host Disease by a Cytotoxic T-Cell Clone That Recognizes Recipient Alloantigens. Blood 91: 4038-4044 [Abstract] [Full Text]
Chai, J.-G., Bartok, I., Scott, D., Dyson, J., Lechler, R. (1998). T:T Antigen Presentation by Activated Murine CD8+ T Cells Induces Anergy and Apoptosis. J. Immunol. 160: 3655-3665 [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]
Sciammas, R., Kodukula, P., Tang, Q., Hendricks, R.L., Bluestone, J.A. (1997). T Cell Receptor-{gamma}/{delta} Cells Protect Mice from Herpes Simplex Virus Type 1-induced Lethal Encephalitis. JEM 185: 1969-1975 [Abstract] [Full Text]
Takeda, S., Shimizu, T., Rodewald, H.-R. (1997). Interactions Between c-kit and Stem Cell Factor Are Not Required for B-Cell Development In Vivo. Blood 89: 518-525 [Abstract] [Full Text]
Harrison, L. C., Dempsey-Collier, M., Kramer, D. R., Takahashi, K. (1996). Aerosol Insulin Induces Regulatory CD8 {gamma}{delta} T Cells That Prevent Murine Insulin-dependent Diabetes. JEM 184: 2167-2174 [Abstract] [Full Text]
Takahama, Y, Shores, E., Singer, A (1992). Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells. Science 258: 653-656 [Abstract]
Philpott, K., Viney, J., Kay, G, Rastan, S, Gardiner, E., Chae, S, Hayday, A., Owen, M. (1992). Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells. Science 256: 1448-1452 [Abstract]
Bleicher, P., Balk, S., Hagen, S., Blumberg, R., Flotte, T., Terhorst, C (1990). Expression of murine CD1 on gastrointestinal epithelium. Science 250: 679-682 [Abstract]
Koller, B., Marrack, P, Kappler, J., Smithies, O (1990). Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248: 1227-1230 [Abstract]