Gamma/delta intraepithelial lymphocytes in the mouse small intestine

Anatomical Science International

Volumn 91, Issue 4, 2016, Pages 301-312

  Ogata, Masaki ^a,b   Itoh, Tsunetoshi ^a,c  

^a TOHOKU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c TOHOKU FUKUSHI UNIVERSITY   (Japan)

Author keywords

DNA fragmentation; Immunohistology; Intraepithelial lymphocyte (IEL); Mouse; Small intestine

Indexed keywords

CD3 ANTIBODY; GRANZYME B; PERFORIN; CD3 ANTIGEN; GRANZYME; MONOCLONAL ANTIBODY;

ACCESSORY CELL; APOPTOSIS; CELL DEATH; CYTOTOXICITY; DEGRANULATION; DIARRHEA; DNA FRAGMENTATION; DUODENUM; FLOW CYTOMETRY; GAMMA DELTA INTRAEPITHELIAL LYMPHOCYTE; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; INTESTINE CELL; INTESTINE EPITHELIUM CELL; JEJUNUM; LYMPHOCYTE; MICROENVIRONMENT; MOUSE; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SMALL INTESTINE; ANATOMY AND HISTOLOGY; ANIMAL; CYTOLOGY; EPITHELIUM CELL; IMMUNOLOGY; LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD3; CELL DEATH; CELL DEGRANULATION; DNA FRAGMENTATION; EPITHELIAL CELLS; GRANZYMES; INTESTINE, SMALL; LYMPHOCYTE ACTIVATION; LYMPHOCYTES; MICE; PERFORIN;

EID: 84964034106     PISSN: 14476959     EISSN: 1447073X     Source Type: Journal    
DOI: 10.1007/s12565-016-0341-2     Document Type: Review

References (114)

1. Allison JP, Havran WL (1991) The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol 9:679–705
2. Andegeko Y, Moyal L, Mittelman L, Tsarfaty I, Shiloh Y, Rotman G (2001) Nuclear retention of ATM at sites of DNA double strand breaks. J Biol Chem 276:38224–38230
3. Baker MB, Altman NH, Podack ER, Levy RB (1996) The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice. J Exp Med 183:2645–2656
4. Barry M, Bleackley RC (2002) Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol 2:401–409
5. Beagley KW, Husband AJ (1998) Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 18:237–254
6. Beagley KW, Fujihashi K, Lagoo AS, Lagoo-Deenadaylan S, Black CA, Murray AM, Sharmanov AT, Yamamoto M, McGhee JR, Elson CO et al (1995) Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine. J Immunol 154:5611–5619
7. Boismenu R, Havran WL (1994) Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science 266:1253–1255
8. Bos JD, Teunissen MB, Cairo I, Krieg SR, Kapsenberg ML, Das PK, Borst J (1990) T-cell receptor gamma delta bearing cells in normal human skin. J Invest Dermatol 94:37–42
9. Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D (1991) Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod 6:791–798
10. Camerini V, Panwala C, Kronenberg M (1993) Regional specialization of the mucosal immune system. Intraepithelial lymphocytes of the large intestine have a different phenotype and function than those of the small intestine. J Immunol 151:1765–1776
11. Chamberlain CM, Ang LS, Boivin WA, Cooper DM, Williams SJ, Zhao H, Hendel A, Folkesson M, Swedenborg J, Allard MF, McManus BM, Granville DJ (2010) Perforin-independent extracellular granzyme B activity contributes to abdominal aortic aneurysm. Am J Pathol 176:1038–1049
12. Chang JS, Ocvirk S, Berger E, Kisling S, Binder U, Skerra A, Lee AS, Haller D (2012) Endoplasmic reticulum stress response promotes cytotoxic phenotype of CD8αβ+ intraepithelial lymphocytes in a mouse model for Crohn’s disease-like ileitis. J Immunol 189:1510–1520
13. Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R (2002) Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci 99:14338–14343
14. Chieppa M, Rescigno M, Huang AY, Germain RN (2006) Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med 203:2841–2852
15. Choy JC, Hung VH, Hunter AL, Cheung PK, Motyka B, Goping IS, Sawchuk T, Bleackley RC, Podor TJ, McManus BM, Granville DJ (2004) Granzyme B induces smooth muscle cell apoptosis in the absence of perforin: involvement of extracellular matrix degradation. Arterioscler Thromb Vasc Biol 24:2245–2250
16. Choy JC, Cruz RP, Kerjner A, Geisbrecht J, Sawchuk T, Fraser SA, Hudig D, Bleackley RC, Jirik FR, McManus BM, Granville DJ (2005) Granzyme B induces endothelial cell apoptosis and contributes to the development of transplant vascular disease. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 5:494–499
17. Corazza N, Muller S, Brunner T, Kagi D, Mueller C (2000) Differential contribution of Fas- and perforin-mediated mechanisms to the cell-mediated cytotoxic activity of naive and in vivo-primed intestinal intraepithelial lymphocytes. J Immunol 164:398–403
18. Darlington D, Rogers AW (1966) Epithelial lymphocytes in the small intestine of the mouse. J Anat 100:813–830
19. Dressel R, Raja SM, Honing S, Seidler T, Froelich CJ, von Figura K, Gunther E (2004) Granzyme-mediated cytotoxicity does not involve the mannose 6-phosphate receptors on target cells. J Biol Chem 279:20200–20210
20. Ebert LM, Meuter S, Moser B (2006) Homing and function of human skin gammadelta T cells and NK cells: relevance for tumor surveillance. J Immunol 176:4331–4336
21. Edelblum KL, Shen L, Weber CR, Marchiando AM, Clay BS, Wang Y, Prinz I, Malissen B, Sperling AI, Turner JR (2012) Dynamic migration of gammadelta intraepithelial lymphocytes requires occludin. Proc Natl Acad Sci 109:7097–7102
22. Falck J, Coates J, Jackson SP (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434:605–611
23. Fehniger TA, Cai SF, Cao X, Bredemeyer AJ, Presti RM, French AR, Ley TJ (2007) Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity 26:798–811
24. Ferguson A (1977) Intraepithelial lymphocytes of the small intestine. Gut 18:921–937
25. Fernandez-Capetillo O, Allis CD, Nussenzweig A (2004) Phosphorylation of histone H2B at DNA double-strand breaks. J Exp Med 199:1671–1677
26. Foster CA, Yokozeki H, Rappersberger K, Koning F, Volc-Platzer B, Rieger A, Coligan JE, Wolff K, Stingl G (1990) Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor. J Exp Med 171:997–1013
27. Frank-Vaillant M, Marcand S (2002) Transient stability of DNA ends allows nonhomologous end joining to precede homologous recombination. Mol Cell 10:1189–1199
28. Froelich CJ, Orth K, Turbov J, Seth P, Gottlieb R, Babior B, Shah GM, Bleackley RC, Dixit VM, Hanna W (1996) New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis. J Biol Chem 271:29073–29079
29. Frossard CP, Asigbetse KE, Burger D, Eigenmann PA (2015) Gut T cell receptor-γδ(+) intraepithelial lymphocytes are activated selectively by cholera toxin to break oral tolerance in mice. Clin Exp Immunol 180:118–130
30. Fujihashi K, Taguchi T, Aicher WK, McGhee JR, Bluestone JA, Eldridge JH, Kiyono H (1992) Immunoregulatory functions for murine intraepithelial lymphocytes: gamma/delta T cell receptor-positive (TCR +) T cells abrogate oral tolerance, while alpha/beta TCR+ T cells provide B cell help. J Exp Med 175:695–707
31. Fujihashi K, Dohi T, Kweon MN, McGhee JR, Koga T, Cooper MD, Tonegawa S, Kiyono H (1999) Gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion. Int Immunol 11:1907–1916
32. Goodman T, Lefrancois L (1988) Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 333:855–858
33. Guy-Grand D, Griscelli C, Vassalli P (1978) The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med 148:1661–1677
34. Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P (1991a) Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med 173:471–481
35. Guy-Grand D, Malassis-Seris M, Briottet C, Vassalli P (1991b) Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med 173:1549–1552
36. Guy-Grand D, DiSanto JP, Henchoz P, Malassis-Seris M, Vassalli P (1998) Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal. Eur J Immunol 28:730–744
37. Guy-Grand D, Vassalli P, Eberl G, Pereira P, Burlen-Defranoux O, Lemaitre F, Di Santo JP, Freitas AA, Cumano A, Bandeira A (2013) Origin, trafficking, and intraepithelial fate of gut-tropic T cells. J Exp Med 210:1839–1854
38. Halvorsen R, Leivestad T, Gaudernack G, Thorsby E (1988) Role of accessory cells in the activation of pure T cells via the T cell receptor-CD3 complex or with phytohaemagglutinin. Scand J Immunol 27:555–563
39. Havran WL, Jameson JM, Witherden DA (2005) Epithelial cells and their neighbors. III. Interactions between intraepithelial lymphocytes and neighboring epithelial cells. Am J Physiol Gastrointest Liver Physiol 289:G627–G630
40. Hayday A, Theodoridis E, Ramsburg E, Shires J (2001) Intraepithelial lymphocytes: exploring the Third Way in immunology. Nat Immunol 2:997–1003
41. Holoshitz J, Romzek NC, Jia Y, Wagner L, Vila LM, Chen SJ, Wilson JM, Karp DR (1993) MHC-independent presentation of mycobacteria to human gamma delta T cells. Int Immunol 5:1437–1443
42. Holtmeier W, Pfander M, Hennemann A, Zollner TM, Kaufmann R, Caspary WF (2001) The TCR-delta repertoire in normal human skin is restricted and distinct from the TCR-delta repertoire in the peripheral blood. J Invest Dermatol 116:275–280
43. Inagaki-Ohara K, Chinen T, Matsuzaki G, Sasaki A, Sakamoto Y, Hiromatsu K, Nakamura-Uchiyama F, Nawa Y, Yoshimura A (2004) Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation. J Immunol 173:1390–1398
44. Ishikawa H, Li Y, Abeliovich A, Yamamoto S, Kaufmann SH, Tonegawa S (1993) Cytotoxic and interferon gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are strain dependent. Proc Natl Acad Sci 90:8204–8208
45. Ismail AS, Behrendt CL, Hooper LV (2009) Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury. J Immunol 182:3047–3054
46. Ismail AS, Severson KM, Vaishnava S, Behrendt CL, Yu X, Benjamin JL, Ruhn KA, Hou B, DeFranco AL, Yarovinsky F, Hooper LV (2011) Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. Proc Natl Acad Sci 108:8743–8748
47. Itohara S, Farr AG, Lafaille JJ, Bonneville M, Takagaki Y, Haas W, Tonegawa S (1990) Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature 343:754–757
48. Jackson SP (2002) Sensing and repairing DNA double-strand breaks. Carcinogenesis 23:687–696
49. Jameson J, Havran WL (2007) Skin gammadelta T-cell functions in homeostasis and wound healing. Immunol Rev 215:114–122
50. Jameson J, Ugarte K, Chen N, Yachi P, Fuchs E, Boismenu R, Havran WL (2002) A role for skin gammadelta T cells in wound repair. Science 296:747–749
51. Jameson JM, Cauvi G, Witherden DA, Havran WL (2004) A keratinocyte-responsive gamma delta TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis. J Immunol 172:3573–3579
52. Jameson JM, Cauvi G, Sharp LL, Witherden DA, Havran WL (2005) Gammadelta T cell-induced hyaluronan production by epithelial cells regulates inflammation. J Exp Med 201:1269–1279
53. Janeway CA Jr, Jones B, Hayday A (1988) Specificity and function of T cells bearing gamma delta receptors. Immunol Today 9:73–76
54. Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen KJ, Podack ER, Zinkernagel RM, Hengartner H (1994) Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369:31–37
55. Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA (1997) Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance. J Immunol 158:3610–3618
56. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–254
57. King A, Loke YW (1990) Uterine large granular lymphocytes: a possible role in embryonic implantation? Am J Obstet Gynecol 162:308–310
58. King DP, Hyde DM, Jackson KA, Novosad DM, Ellis TN, Putney L, Stovall MY, Van Winkle LS, Beaman BL, Ferrick DA (1999) Cutting edge: protective response to pulmonary injury requires gamma delta T lymphocytes. J Immunol 162:5033–5036
59. Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S et al (1995) Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci 92:6147–6151
60. Komori HK, Meehan TF, Havran WL (2006) Epithelial and mucosal gamma delta T cells. Curr Opin Immunol 18:534–538
61. Laky K, Lefrancois L, Lingenheld EG, Ishikawa H, Lewis JM, Olson S, Suzuki K, Tigelaar RE, Puddington L (2000) Enterocyte expression of interleukin 7 induces development of gammadelta T cells and Peyer’s patches. J Exp Med 191:1569–1580
62. Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308:551–554
63. Lee JH, Paull TT (2006) Purification and biochemical characterization of ataxia-telangiectasia mutated and Mre11/Rad50/Nbs1. Methods Enzymol 408:529–539
64. Lee JH, Paull TT (2007) Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 26:7741–7748
65. Lee SH, Bar-Haim E, Machlenkin A, Goldberger O, Volovitz I, Vadai E, Tzehoval E, Eisenbach L (2004) In vivo rejection of tumor cells dependent on CD8 cells that kill independently of perforin and FasL. Cancer Gene Ther 11:237–248
66. Lin T, Brunner T, Tietz B, Madsen J, Bonfoco E, Reaves M, Huflejt M, Green DR (1998) Fas ligand-mediated killing by intestinal intraepithelial lymphocytes. Participation in intestinal graft-versus-host disease. J Clin Investig 101:570–577
67. Lowin B, Hahne M, Mattmann C, Tschopp J (1994) Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370:650–652
68. Mayrhofer G (1980) Thymus-dependent and thymus-independent subpopulations of intestinal intraepithelial lymphocytes: a granular subpopulation of probable bone marrow origin and relationship to mucosal mast cells. Blood 55:532–535
69. Mengel J, Cardillo F, Aroeira LS, Williams O, Russo M, Vaz NM (1995) Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice. Immunol Lett 48:97–102
70. Mollick JA, Cook RG, Rich RR (1989) Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. Science 244:817–820
71. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR, Golan DE, Brenner MB (1995) Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity 3:495–507
72. Motyka B, Korbutt G, Pinkoski MJ, Heibein JA, Caputo A, Hobman M, Barry M, Shostak I, Sawchuk T, Holmes CF, Gauldie J, Bleackley RC (2000) Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell 103:491–500
73. Mowat AM (2003) Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 3:331–341
74. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258
75. Ogata M, Oomori T, Soga H, Ota Y, Itoh A, Matsutani T, Nanno M, Suzuki R, Itoh T (2009) DNA repair after DNA fragmentation in mouse small intestinal epithelial cells. Cell Tissue Res 335:371–382
76. Ogata M, Ota Y, Matsutani T, Nanno M, Suzuki R, Itoh T (2013) Granzyme B-dependent and perforin-independent DNA fragmentation in intestinal epithelial cells induced by anti-CD3 mAb-activated intra-epithelial lymphocytes. Cell Tissue Res 352:287–300
77. Ogata M, Ota Y, Nanno M, Suzuki R, Itoh T (2014) Activation of intra-epithelial lymphocytes; their morphology, marker expression and ultimate fate. Cell Tissue Res 356:217–230
78. Ogata M, Ota Y, Nanno M, Suzuki R, Itoh T (2015) Autocrine DNA fragmentation of intra-epithelial lymphocytes (IELs) in mouse small intestine. Cell Tissue Res 361:799–810
79. Pabst O, Bernhardt G (2010) The puzzle of intestinal lamina propria dendritic cells and macrophages. Eur J Immunol 40:2107–2111
80. Panja A, Blumberg RS, Balk SP, Mayer L (1993) CD1d is involved in T cell-intestinal epithelial cell interactions. J Exp Med 178:1115–1119
81. Penney L, Kilshaw PJ, MacDonald TT (1995) Regional variation in the proliferative rate and lifespan of alpha beta TCR+ and gamma delta TCR+ intraepithelial lymphocytes in the murine small intestine. Immunology 86:212–218
82. Pereira P, Gerber D, Huang SY, Tonegawa S (1995) Ontogenic development and tissue distribution of V gamma 1-expressing gamma/delta T lymphocytes in normal mice. J Exp Med 182:1921–1930
83. Porcelli S, Brenner MB, Band H (1991) Biology of the human gamma delta T-cell receptor. Immunol Rev 120:137–183
84. Rapp A, Greulich KO (2004) After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available. J Cell Sci 117:4935–4945
85. Regnier-Vigouroux A, Blanc D, Pont S, Marchetto S, Pierres M (1986) Accessory molecules and T cell activation. I. Antigen receptor avidity differentially influences T cell sensitivity to inhibition by monoclonal antibodies to LFA-1 and L3T4. Eur J Immunol 16:1385–1390
86. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367
87. Richardson C, Jasin M (2000) Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol Cell Biol 20:9068–9075
88. Rock EP, Sibbald PR, Davis MM, Chien YH (1994) CDR3 length in antigen-specific immune receptors. J Exp Med 179:323–328
89. Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146:905–916
90. Rothkamm K, Lobrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low X-ray doses. Proc Natl Acad Sci 100:5057–5062
91. Ruemmele FM, Russo P, Beaulieu J, Dionne S, Levy E, Lentze MJ, Seidman EG (1999) Susceptibility to FAS-induced apoptosis in human nontumoral enterocytes: role of costimulatory factors. J Cell Physiol 181:45–54
92. Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D, Lopez BS (2001) Characterization of homologous recombination induced by replication inhibition in mammalian cells. EMBO J 20:3861–3870
93. Schild H, Mavaddat N, Litzenberger C, Ehrich EW, Davis MM, Bluestone JA, Matis L, Draper RK, Chien YH (1994) The nature of major histocompatibility complex recognition by gamma delta T cells. Cell 76:29–37
94. Sharp LL, Jameson JM, Cauvi G, Havran WL (2005) Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1. Nat Immunol 6:73–79
95. Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH (1997) Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization. J Exp Med 185:855–866
96. Steege JC, Buurman WA, Forget PP (1997) The neonatal development of intraepithelial and lamina propria lymphocytes in the murine small intestine. Dev Immunol 5:121–128
97. Strater J, Wellisch I, Riedl S, Walczak H, Koretz K, Tandara A, Krammer PH, Moller P (1997) CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 113:160–167
98. Sugahara S, Shimizu T, Yoshida Y, Aiba T, Yamagiwa S, Asakura H, Abo T (1999) Extrathymic derivation of gut lymphocytes in parabiotic mice. Immunology 96:57–65
99. Suzuki S, Sugahara S, Shimizu T, Tada T, Minagawa M, Maruyama S, Watanabe H, Saito H, Ishikawa H, Hatakeyama K, Abo T (1998) Low level of mixing of partner cells seen in extrathymic T cells in the liver and intestine of parabiotic mice: its biological implication. Eur J Immunol 28:3719–3729
100. Suzuki H, Jeong KI, Okutani T, Doi K (2000) Regional variations in the number and subsets of intraepithelial lymphocytes in the mouse small intestine. Comp Med 50:39–42
101. Sydora BC, Mixter PF, Houlden B, Hershberg R, Levy R, Comay M, Bluestone J, Kronenberg M (1993) T-cell receptor gamma delta diversity and specificity of intestinal intraepithelial lymphocytes: analysis of IEL-derived hybridomas. Cell Immunol 152:305–322
102. Tamura A, Soga H, Yaguchi K, Yamagishi M, Toyota T, Sato J, Oka Y, Itoh T (2003) Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine. Cell Tissue Res 313:47–53
103. Tang X, Hui ZG, Cui XL, Garg R, Kastan MB, Xu B (2008) A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol Cell Biol 28:2559–2566
104. Targan SR, Deem RL, Liu M, Wang S, Nel A (1995) Definition of a lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway. J Immunol 154:664–675
105. Trapani JA (2012) Granzymes, cytotoxic granules and cell death: the early work of Dr. Jurg Tschopp. Cell Death Differ 19:21–27
106. Trapani JA, Davis J, Sutton VR, Smyth MJ (2000) Proapoptotic functions of cytotoxic lymphocyte granule constituents in vitro and in vivo. Curr Opin Immunol 12:323–329
107. Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H, Tsujikawa K, Yamamoto H (2003) Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol 171:5507–5513
108. Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S (2008) Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 9:769–776
109. Urboniene D, Babusyte A, Lotvall J, Sakalauskas R, Sitkauskiene B (2013) Distribution of gammadelta and other T-lymphocyte subsets in patients with chronic obstructive pulmonary disease and asthma. Respir Med 107:413–423
110. Vroom TM, Scholte G, Ossendorp F, Borst J (1991) Tissue distribution of human gamma delta T cells: no evidence for general epithelial tropism. J Clin Pathol 44:1012–1017
111. Wei S, Gamero AM, Liu JH, Daulton AA, Valkov NI, Trapani JA, Larner AC, Weber MJ, Djeu JY (1998) Control of lytic function by mitogen-activated protein kinase/extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: identification of perforin and granzyme B mobilization by functional ERK2. J Exp Med 187:1753–1765
112. Weintraub BC, Jackson MR, Hedrick SM (1994) Gamma delta T cells can recognize nonclassical MHC in the absence of conventional antigenic peptides. J Immunol 153:3051–3058
113. Yaguchi K, Kayaba S, Soga H, Yamagishi M, Tamura A, Kasahara S, Ohara S, Satoh J, Oka Y, Toyota T, Itoh T (2004) DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes. Cell Tissue Res 315:71–84
114. Yu Q, Tang C, Xun S, Yajima T, Takeda K, Yoshikai Y (2006) MyD88-dependent signaling for IL-15 production plays an important role in maintenance of CD8 alpha alpha TCR alpha beta and TCR gamma delta intestinal intraepithelial lymphocytes. J Immunol 176:6180–6185