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Total Parenteral Nutrition-Associated Changes in Mouse Intestinal Intraepithelial Lymphocytes

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Abstract

Intraepithelial lymphocytes (IEL) play a major role in mucosal defense mechanisms against intraluminal foreign antigens. To address the role luminal nutrients have on the phenotype and function of the IEL, we administered total parenteral nutrition (TPN) to mice, with the absence of enteral intake. We hypothesized that administration of TPN would result in changes in the phenotype and function of the IEL. For this, we utilized a mouse model of TPN. A significant decline in the CD4+ IEL population occurred with TPN. Additionally, the CD8+,CD44+ IEL subset showed a 65% decline (P < 0.05), and the CD4+,CD44+ subset declined by 55% with TPN (P < 0.05). The CD8αβ+ population (a marker of thymic-dependence) also declined by 92% (P < 0.01) with TPN. IEL in the TPN group showed a significantly lower degree of in vitro proliferation. In conclusion, the IEL showed significant phenotypic changes with TPN including the loss of the thymic-derived population. Functionally, the IEL showed a significant decline in proliferation. Such changes demonstrate the important role luminal nutrients have on IEL phenotype and function.

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REFERENCES

  1. Anderson G, Steinberg E: DRG's and specialized nutritional support: the need for reform. J Parenter Enteral Nutr 10:3–10, 1986

    Google Scholar 

  2. Moore F, Moore E, Jones T: TEN vs TPN following major abdominal trauma: Reduced septic morbidity. J Trauma 29:916–923, 1989

    Google Scholar 

  3. Moore F, Feliciano D, Andrassy R, et al: Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg 216:172–183, 1992

    Google Scholar 

  4. Kudsk K, Croce M, Fabian T, et al: Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 215:503–511, 1992

    Google Scholar 

  5. Kurkchubasche AG, Smith SD, Rowe MI: Catheter sepsis in short-bowel syndrome. Arch Surg 127:21–25, 1992

    Google Scholar 

  6. Alexander JW: Nutrition and translocation. J Parenter Enteral Nutr 14:170S–174S, 1990

    Google Scholar 

  7. Johnson LR, Copeland EM, Dudrick SJ, Lichtenberger LM, Castro GA: Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats. Gastroenterology 68:1177–1183, 1975

    Google Scholar 

  8. Buchman A, Moukarzel A, Bhuta S, et al: Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. J Parenter Enteral Nutr 19:453–460, 1995

    Google Scholar 

  9. Deitch E, Xu D, Qi L, Berg R: Elemental diet-induced immune suppression is caused by both bacterial and dietary factors. J Parenter Enteral Nutr 17:332–336, 1993

    Google Scholar 

  10. Hosada N, Nishi M, Nakagawa M: Structural and functional alterations in the gut of parenterally or enterally fed rats. J Surg Res 47:129–133, 1989

    Google Scholar 

  11. Yamamoto M, Fujihashi K, Kawabata K, McGhee J, Kiyono H: A mucosal intranet: Intestinal epithelial cells down-regulate intraepithelial, but not peripheral, T lymphocytes. J Immunol 160:2188–2196, 1998

    Google Scholar 

  12. Teitelbaum D, Reyas B, Merion R, Mosley R: Intestinal intraepithelial lymphocytes: identification of an inhibitory subpopulation. J Surg Res 63:123–127, 1996

    Google Scholar 

  13. Guy-Grand D, Vassalli P: Gut intraepithelial T lymphocytes. Curr Opin Immunol 5:247–252, 1993

    Google Scholar 

  14. Klein J, Mosley R: Phenotypic and Cytotoxic Characteristics of Intraepithelial Lymphocytes, 9 vol. New York; Raven Press, 1994, pp 33–60

    Google Scholar 

  15. Cerf-Bensussan N, Guy-Grand D: Intestinal intraepithelial lymphocytes. Gastroenterol Clin North Am 20:549–576, 1991

    Google Scholar 

  16. LeFrancois L, Lecorre R, Mayo J, Bluestone J, Goodman T: Extrathymic selection of TCR ?? cells by class II major histocompatibility complex molecules. Cell 63:333–340, 1990

    Google Scholar 

  17. Haas W: Gamma/delta cells. Annu Rev Immunol 11:637–685, 1993

    Google Scholar 

  18. Mosley RL, Styre D, Klein JR: Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras. J Immunol 145:1369–1375, 1990

    Google Scholar 

  19. Guy-Grand D, Vassalli P: Origin of gut intraepithelial lymphocytes. Immunol Res 10:296–301, 1991

    Google Scholar 

  20. Rocha B, Vassalli P, Guy-Grand D: Thymic and extrathymic origins of the gut intraepithelial lymphocyte populations in mice. J Exp Med 180:681–686, 1994

    Google Scholar 

  21. Teitelbaum D, Narasimhan A, Chenault R, Merion R: Lymphocyte immunologic interactions in intestinal transplantation. Transplant Proc 26:1525–1526, 1994

    Google Scholar 

  22. Beagley KW, Fujihashi K, Black CA, et al: The Mycobacterium tuberculosis 71-kDa heat-shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes. Eur J Immunol 23:2049–2052, 1993

    Google Scholar 

  23. Ebert EC: Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli. Gastroenterology 97:1372–1381, 1989

    Google Scholar 

  24. Mowat AM, MacKenzie S, Baca ME, Felstein MV, Parrott DM: Functional characteristics of intraepithelial lymphocytes from mouse small intestine. II. In vivo and in vitro responses of intraepithelial lymphocytes to mitogenic and allogeneic stimuli. Immunology 58:627–634, 1986

    Google Scholar 

  25. Nakamura T, Matsuzaki G, Takimoto H, Nomoto K: Ageassociated changes in the proliferative response of rat intestinal intraepithelial leukocytes to bacterial antigens. Gastroenterology 109:748–754, 1995

    Google Scholar 

  26. Mosley RL, Styre D, Klein JR: Immune recognition by cytotoxic T lymphocytes of minor histocompatibility antigens expressed on a murine colon carcinoma line. Cell Immunol 122:200–207, 1989

    Google Scholar 

  27. Ebert E: Intra-epithelial lymphocytes: Interferon-gamma production and suppressor/cytotoxic activities. Clin Exp Immunol 82:81–85, 1990

    Google Scholar 

  28. Whary MT, Zarkower A, Confer FL, Ferguson FG: Agerelated differences in subset composition and activation responses of intestinal intraepithelial and mesenteric lymph node lymphocytes from neonatal swine. Cell Immunol 163:215–221, 1995

    Google Scholar 

  29. Regnault A, Levraud JP, Lim A, et al: The expansion and selection of T cell receptor alpha beta intestinal intraepithelial T cell clones. Eur J Immunol 26:914–921, 1996

    Google Scholar 

  30. Chandra RK, Wadhwa M: Nutritional modulation of intestinal mucosal immunity. Immunol Invest 18:119–126, 1989

    Google Scholar 

  31. Boismenu R, Havran WL: Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science 266:1253–1255, 1994

    Google Scholar 

  32. Li J, Kudsk KA, Gocinski B, Dent D, Glezer J, Langkamp-Henken B: Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. The Journal of Trauma: Injury Infect Crit Care 39:44–52, 1995

    Google Scholar 

  33. Mosley RL, Klein JR: A rapid method for isolating murine intestine intraepithelial lymphocytes with high yield and purity. J Immunol Methods 156:19–26, 1992

    Google Scholar 

  34. Dozmorov IM, Miller RA: Regulatory interactions between virgin and memory CD4 T lymphocytes. Cell Immunol 172:141–148, 1996

    Google Scholar 

  35. Urao M, Teitelbaum D, Drongowski R, Coran A: The effect of gut-associated lymphoid tissue (GALT) on bacterial translocation in the newborn rabbit. J Pediatr Surg 31:1–7, 1996

    Google Scholar 

  36. Shapiro H: Practical Flow Cytometry, 2nd ed. New York, Alan R. Liss, 1988

    Google Scholar 

  37. Dozmorov IM, Kalinichenko VV, Sidorov IA, Miller RA: Antagonistic interactions among T cell subsets of old mice revealed by limiting dilution analysis. J Immunol 154:4283–4293, 1995

    Google Scholar 

  38. Alverdy JC, Aoys E, Moss GS: Total parenteral nutrition promotes bacterial translocation from the gut. Surgery 104:185–190, 1988

    Google Scholar 

  39. Mainous M, Xu DZ, Lu Q, Berg RD, Deitch EA: Oral-TPNinduced bacterial translocation and impaired immune defenses are reversed by refeeding. Surgery 110:277–283; discussion 283–284, 1991

    Google Scholar 

  40. Kudsk KA, Li J, Renegar KB: Loss of upper respiratory tract immunity with parenteral feeding. Ann Surg 223:629–635; discussion 635–638, 1996

    Google Scholar 

  41. Guihot G, Merle V, Leborgne M, et al: Enteral nutrition modifies gut-associated lymphoid tissue in rat regardless of the molecular form of nitrogen supply. J Pediatr Gastroenterol Nut 24:153–161, 1997

    Google Scholar 

  42. Ganessunker D, Gaskins HR, Zuckermann FA, Donovan SM: Total parenteral nutrition alters molecular and cellular indices of intestinal inflammation in neonatal piglets. JPEN 23:337–344, 1999

    Google Scholar 

  43. Taguchi T, Aicher WK, Fujihashi K, et al: Novel function for intestinal intraepithelial lymphocytes. Murine CD3+, ?? TCR+ T cells produce IFN-? and IL-5. J Immunol 147:3736–3744, 1991

    Google Scholar 

  44. Takahashi I, Nakagawa I, Kiyono H, McGhee JR, Clements JD, Hamada S: Mucosal T cells induce systemic anergy for oral tolerance. Biochem Biophys Res Commun 206:414–420, 1995

    Google Scholar 

  45. Lefrancois L: Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J Immunol 147:1746–1751, 1991

    Google Scholar 

  46. Goodman T, Lefrancois L. Expression of the ??-T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 333:855–858, 1988

    Google Scholar 

  47. Mosley RL, Klein JR: Repopulation kinetics of intestinal intraepithelial lymphocytes in murine bone marrow radiation chimeras. Transplantation 53:868–874, 1992

    Google Scholar 

  48. Lefrancois L: Extrathymic differentiation of intraepithelial lymphocytes: Generation of a separate and unequal T-cell repertoire? Immunol Today 12:436–438, 1991

    Google Scholar 

  49. Takimoto H, Nakamura T, Takeuchi M, et al: Age-associated increase in number of CD4+CD8+ intestinal intraepithelial lymphocytes in rats. Eur J Immunol 22:159–164, 1992

    Google Scholar 

  50. Seibold F, Seibold-Schmid B, Cong Y, Shu F, McCabe R, Weaver, C, Elson C: Regional differences in L-selectin expression in murine intestinal lymphocytes. Gastroenterology 114:965–974, 1998

    Google Scholar 

  51. Lefrancois L: Carbohydrate differentiation antigens on murine T cells: expression of intestinal lymphocytes and intestinal epithelium. J Immunol 138:3375–3384, 1987

    Google Scholar 

  52. Holcombe H, Tonkonogy S: Murine intestinal intraepithelial lymphocytes contain CD8+ cells that produce IL-2 and INF-? but not IL-4. FASEB J 5:1781, 1991

    Google Scholar 

  53. Maloy KJ, Mowat AM, Zamoyska R, Crispe IN: Phenotypic heterogeneity of intraepithelial T lymphocytes from mouse small intestine. Immunology 72:555–562, 1991

    Google Scholar 

  54. Ernst DN, Weigle WO, McQuitty DN, Rothermel AL, Hobbs MV: Stimulation of murine T cell subsets with anti-CD3 antibody. Age-related defects in the expression of early activation molecules. J Immunol 142:1413–1421, 1989

    Google Scholar 

  55. Ernst DN, Weigle O, Hobbs MV: Aging and lymphokine gene expression by T cell subsets. Nutr Rev 53:S18–S25; discussion S25–S26, 1995

    Google Scholar 

  56. DeGrendele HC, Estess P, Siegelman MH: Requirement for CD44 in activated T cell extravasation into an inflammatory site. Science 278:672–675, 1997

    Google Scholar 

  57. Crabbe P, Brazin H, Eyssen H, Heremans J: The normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing IgA in the gut. The germ-free intestinal tract. Int Arch Allergy Appl Immunol 34:362–375, 1968

    Google Scholar 

  58. Umesaki Y, Setoyama H, Matsumoto S, Okada Y: Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology 79:32–37, 1993

    Google Scholar 

  59. Steege J, Buurman W, Forget P: The neontal development of intraepithelial and lamina propria lymphocytes in the murine small intestine. Dev Immunol 5:121–128, 1997

    Google Scholar 

  60. Umesaki Y, Okada Y, Matsumoto S, Imaoka A, Setoyama H: Segmented filamentous bacteria are indigenous intestinal bacteria that activate intraepithelial lymphocytes and induce MHC class II molecules and fucosyl asialo GM1 glycolipids on the small intestinal epithelial cells in the ex-germ-free mouse. Microbiol Immunol 39:555–562, 1995

    Google Scholar 

  61. Kirjavainen PV, El-Nezami HS, Salminen SJ, Ahokas JT, Wright PF: The effect of orally administered viable probiotic and dairy lactobacilli on mouse lymphocyte proliferation. FEMS Immunol Med Microbiol 26:131–135, 1999

    Google Scholar 

  62. Herias MV, Hessle C, Telemo E, Midtvedt T, Hanson LA, Wold AE: Immunomodulatory effects of Lactobacillus plantarum colonizing the intestine of gnotobiotic rats. Clin Exp Immunol 116:283–290, 1999

    Google Scholar 

  63. Guy-Grand D, Malassis-Seris M, Briottet C, Vassalli P: 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, 1991

    Google Scholar 

  64. Klein JR. Ontogeny of the Thy-1-, Lyt-2+ murine intestinal intraepithelial lymphocyte. Characterization of a unique population of thymus-independent cytotoxic effector cells in the intestinal mucosa. J Exp Med 164:309–314, 1986

    Google Scholar 

  65. Kenai H, Matsuzaki G, Nakamura T, Yoshikai Y, Nomoto K: Thymus-derived cytokine(s) including interleukin-7 induce increase of T cell receptor ??+ CD4-CD8- T cells which are extrathymically differentiated in athymic nude mice. Eur J Immunol 23:1818–1825, 1993

    Google Scholar 

  66. Lefrancois L, Puddington L: Extrathymic intestinal T-cell development: Virtual reality? Immunol Today 16:16–21, 1995

    Google Scholar 

  67. Ibraghimov AR, Lynch RG: Heterogeneity and biased T cell receptor alpha/beta repertoire of mucosal CD8+ cells from murine large intestine: implications for functional state. J Exp Med 180:433–444, 1994

    Google Scholar 

  68. Kiristioglu I, Teitelbaum DH: Alteration of the intestinal intraepithelial lymphocytes during total parenteral nutrition. J Surg Res 79:91–96, 1998

    Google Scholar 

  69. Ayala A, Herdon C, Lehman D, DeMaso C, Ayala C, Chaudry I: The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor. Shock 3:259–267, 1995

    Google Scholar 

  70. Ayala A, Xu YX, Chung CS, Chaudry IH. Does Fas ligand or endotoxin contribute to thymic apoptosis during polymicrobial sepsis? Shock 11:211–217, 1999

    Google Scholar 

  71. Das G, Janeway C: 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, 1999

    Google Scholar 

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Kiristioglu, I., Antony, P., Fan, Y. et al. Total Parenteral Nutrition-Associated Changes in Mouse Intestinal Intraepithelial Lymphocytes. Dig Dis Sci 47, 1147–1157 (2002). https://doi.org/10.1023/A:1015066813675

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