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. 1996 Oct;89(2):227–237. doi: 10.1046/j.1365-2567.1996.d01-727.x

Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue.

I N Farstad 1, T S Halstensen 1, B Lien 1, P J Kilshaw 1, A I Lazarovits 1, P Brandtzaeg 1, A I Lazarovitz 1
PMCID: PMC1456483  PMID: 8943719

Abstract

Two alternative integrins involved in mucosal homing (alpha 4 beta 7) or epithelial retention (alpha E beta 7) of lymphocytes were examined in the human gut. The distribution of the beta 7 subunit [monoclonal antibody (mAb) M301] was bimodal in that it was strongly expressed by alpha E beta 7 + cells but weakly by alpha 4 beta 7 + cells. More than 90% of intraepithelial lymphocytes (IEL), including the minor subsets of CD4+, T-cell receptor (TCR) gamma/delta +, and CD3- cells, expressed alpha E beta 7 as did most lamina propria CD8+ (88%) and a fraction (36%) of CD4+ lymphocytes. Conversely, B-lineage cells (CD19+) and macrophages (CD68+) were negative. In gut-associated lymphoid tissue (GALT: Peyer's patches and appendix) only a few (< 5%) cells were positive for alpha E beta 7 (confined to CD8+ lymphocytes and CD11c+ putative dendritic cells). A relatively small fraction of IEL (30-50%) expressed alpha 4 beta 7 (mAb Act-1), while most (70%) lamina propria T and B lymphocytes, blasts, plasma cells and macrophages were positive. In GALT, T lymphocytes expressed similar levels of alpha 4 beta 7 as in the lamina propria whereas relatively few B lymphocytes (< 50%) were positive. Isolated lamina propria CD8+, CD4+, CD19+, and CD38+ cells contained mRNA for alpha 4 and the former three subsets as well as appendix CD8+ cells also for beta 7 while only lamina propria CD8+ cells had mRNA for alpha E. Together, the results suggested that alpha E beta 7 and alpha 4 beta 7 are differentially regulated in inductive sites and effector sites of the human gut. Because lymphoid cells at both sites expressed mainly alpha 4 beta 7, this integrin may be a homing receptor on memory and effector cells bound for lamina propria as well as on naive lymphocytes extravasating in GALT. Conversely, because alpha E beta 7 was mainly expressed by CD8+ cells in epithelium and lamina propria, it was probably induced after extravasation, in agreement with the observation that IEL and a fraction of lamina propria T lymphocytes (mainly CD8+ cells) generally expressed higher levels of beta 7 than most CD4+ and B cells. Also a subset of putative dendritic cells located near the follicle-associated epithelium of GALT expressed alpha E beta 7, perhaps reflecting epithelial interaction during primary immune responses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bargatze R. F., Jutila M. A., Butcher E. C. Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined. Immunity. 1995 Jul;3(1):99–108. doi: 10.1016/1074-7613(95)90162-0. [DOI] [PubMed] [Google Scholar]
  2. Barnard J. A., Beauchamp R. D., Coffey R. J., Moses H. L. Regulation of intestinal epithelial cell growth by transforming growth factor type beta. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1578–1582. doi: 10.1073/pnas.86.5.1578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  4. Bjerke K., Brandtzaeg P. Lack of relation between expression of HLA-DR and secretory component (SC) in follicle-associated epithelium of human Peyer's patches. Clin Exp Immunol. 1988 Mar;71(3):502–507. [PMC free article] [PubMed] [Google Scholar]
  5. Bjerke K., Halstensen T. S., Jahnsen F., Pulford K., Brandtzaeg P. Distribution of macrophages and granulocytes expressing L1 protein (calprotectin) in human Peyer's patches compared with normal ileal lamina propria and mesenteric lymph nodes. Gut. 1993 Oct;34(10):1357–1363. doi: 10.1136/gut.34.10.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cepek K. L., Parker C. M., Madara J. L., Brenner M. B. Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol. 1993 Apr 15;150(8 Pt 1):3459–3470. [PubMed] [Google Scholar]
  7. Cepek K. L., Shaw S. K., Parker C. M., Russell G. J., Morrow J. S., Rimm D. L., Brenner M. B. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. Nature. 1994 Nov 10;372(6502):190–193. doi: 10.1038/372190a0. [DOI] [PubMed] [Google Scholar]
  8. Cerf-Bensussan N., Bègue B., Gagnon J., Meo T. The human intraepithelial lymphocyte marker HML-1 is an integrin consisting of a beta 7 subunit associated with a distinctive alpha chain. Eur J Immunol. 1992 Jan;22(1):273–277. doi: 10.1002/eji.1830220140. [DOI] [PubMed] [Google Scholar]
  9. Cerf-Bensussan N., Jarry A., Brousse N., Lisowska-Grospierre B., Guy-Grand D., Griscelli C. A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. Eur J Immunol. 1987 Sep;17(9):1279–1285. doi: 10.1002/eji.1830170910. [DOI] [PubMed] [Google Scholar]
  10. Chan B. M., Elices M. J., Murphy E., Hemler M. E. Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY. J Biol Chem. 1992 Apr 25;267(12):8366–8370. [PubMed] [Google Scholar]
  11. Craig S. W., Cebra J. J. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med. 1971 Jul 1;134(1):188–200. doi: 10.1084/jem.134.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cuff C. F., Cebra C. K., Rubin D. H., Cebra J. J. Developmental relationship between cytotoxic alpha/beta T cell receptor-positive intraepithelial lymphocytes and Peyer's patch lymphocytes. Eur J Immunol. 1993 Jun;23(6):1333–1339. doi: 10.1002/eji.1830230622. [DOI] [PubMed] [Google Scholar]
  13. Erle D. J., Briskin M. J., Butcher E. C., Garcia-Pardo A., Lazarovits A. I., Tidswell M. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. J Immunol. 1994 Jul 15;153(2):517–528. [PubMed] [Google Scholar]
  14. Erle D. J., Rüegg C., Sheppard D., Pytela R. Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes. J Biol Chem. 1991 Jun 15;266(17):11009–11016. [PubMed] [Google Scholar]
  15. Farstad I. N., Halstensen T. S., Fausa O., Brandtzaeg P. Do human Peyer's patches contribute to the intestinal intraepithelial gamma/delta T-cell population? Scand J Immunol. 1993 Nov;38(5):451–458. doi: 10.1111/j.1365-3083.1993.tb02587.x. [DOI] [PubMed] [Google Scholar]
  16. Farstad I. N., Halstensen T. S., Fausa O., Brandtzaeg P. Heterogeneity of M-cell-associated B and T cells in human Peyer's patches. Immunology. 1994 Nov;83(3):457–464. [PMC free article] [PubMed] [Google Scholar]
  17. Farstad I. N., Halstensen T. S., Lazarovits A. I., Norstein J., Fausa O., Brandtzaeg P. Human intestinal B-cell blasts and plasma cells express the mucosal homing receptor integrin alpha 4 beta 7. Scand J Immunol. 1995 Dec;42(6):662–672. doi: 10.1111/j.1365-3083.1995.tb03709.x. [DOI] [PubMed] [Google Scholar]
  18. Guy-Grand D., Griscelli C., Vassalli P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol. 1974 Jun;4(6):435–443. doi: 10.1002/eji.1830040610. [DOI] [PubMed] [Google Scholar]
  19. Hamann A., Andrew D. P., Jablonski-Westrich D., Holzmann B., Butcher E. C. Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994 Apr 1;152(7):3282–3293. [PubMed] [Google Scholar]
  20. Hu M. C., Crowe D. T., Weissman I. L., Holzmann B. Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's patch-specific lymphocyte homing. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8254–8258. doi: 10.1073/pnas.89.17.8254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  22. Karecla P. I., Bowden S. J., Green S. J., Kilshaw P. J. Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7). Eur J Immunol. 1995 Mar;25(3):852–856. doi: 10.1002/eji.1830250333. [DOI] [PubMed] [Google Scholar]
  23. Kelleher D., Murphy A., Lynch S., O'Farrelly C. Adhesion molecules utilized in binding of intraepithelial lymphocytes to human enterocytes. Eur J Immunol. 1994 Apr;24(4):1013–1016. doi: 10.1002/eji.1830240437. [DOI] [PubMed] [Google Scholar]
  24. Kilshaw P. J. Expression of the mucosal T cell integrin alpha M290 beta 7 by a major subpopulation of dendritic cells in mice. Eur J Immunol. 1993 Dec;23(12):3365–3368. doi: 10.1002/eji.1830231246. [DOI] [PubMed] [Google Scholar]
  25. Kilshaw P. J., Murant S. J. Expression and regulation of beta 7(beta p) integrins on mouse lymphocytes: relevance to the mucosal immune system. Eur J Immunol. 1991 Oct;21(10):2591–2597. doi: 10.1002/eji.1830211041. [DOI] [PubMed] [Google Scholar]
  26. Lazarovits A. I., Moscicki R. A., Kurnick J. T., Camerini D., Bhan A. K., Baird L. G., Erikson M., Colvin R. B. Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen. J Immunol. 1984 Oct;133(4):1857–1862. [PubMed] [Google Scholar]
  27. Parker C. M., Cepek K. L., Russell G. J., Shaw S. K., Posnett D. N., Schwarting R., Brenner M. B. A family of beta 7 integrins on human mucosal lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1924–1928. doi: 10.1073/pnas.89.5.1924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pinola M., Saksela E., Tiisala S., Renkonen R. Human NK cells expressing alpha 4 beta 1/beta 7 adhere to VCAM-1 without preactivation. Scand J Immunol. 1994 Feb;39(2):131–136. doi: 10.1111/j.1365-3083.1994.tb03351.x. [DOI] [PubMed] [Google Scholar]
  29. Postigo A. A., Sánchez-Mateos P., Lazarovits A. I., Sánchez-Madrid F., de Landázuri M. O. Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes. J Immunol. 1993 Sep 1;151(5):2471–2483. [PubMed] [Google Scholar]
  30. Rott L. S., Briskin M. J., Andrew D. P., Berg E. L., Butcher E. C. A fundamental subdivision of circulating lymphocytes defined by adhesion to mucosal addressin cell adhesion molecule-1. Comparison with vascular cell adhesion molecule-1 and correlation with beta 7 integrins and memory differentiation. J Immunol. 1996 May 15;156(10):3727–3736. [PubMed] [Google Scholar]
  31. Schieferdecker H. L., Ullrich R., Weiss-Breckwoldt A. N., Schwarting R., Stein H., Riecken E. O., Zeitz M. The HML-1 antigen of intestinal lymphocytes is an activation antigen. J Immunol. 1990 Apr 1;144(7):2541–2549. [PubMed] [Google Scholar]
  32. Schweighoffer T., Tanaka Y., Tidswell M., Erle D. J., Horgan K. J., Luce G. E., Lazarovits A. I., Buck D., Shaw S. Selective expression of integrin alpha 4 beta 7 on a subset of human CD4+ memory T cells with Hallmarks of gut-trophism. J Immunol. 1993 Jul 15;151(2):717–729. [PubMed] [Google Scholar]
  33. Shimizu Y., Newman W., Tanaka Y., Shaw S. Lymphocyte interactions with endothelial cells. Immunol Today. 1992 Mar;13(3):106–112. doi: 10.1016/0167-5699(92)90151-V. [DOI] [PubMed] [Google Scholar]
  34. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  35. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  36. Streeter P. R., Berg E. L., Rouse B. T., Bargatze R. F., Butcher E. C. A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature. 1988 Jan 7;331(6151):41–46. doi: 10.1038/331041a0. [DOI] [PubMed] [Google Scholar]
  37. Tiisala S., Paavonen T., Renkonen R. Alpha E beta 7 and alpha 4 beta 7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages. Eur J Immunol. 1995 Feb;25(2):411–417. doi: 10.1002/eji.1830250216. [DOI] [PubMed] [Google Scholar]
  38. Visser L., Poppema S. Induction of B-cell chronic lymphocytic leukaemia and hairy cell leukaemia like phenotypes by phorbol ester treatment of normal peripheral blood B-cells. Br J Haematol. 1990 Jul;75(3):359–365. doi: 10.1111/j.1365-2141.1990.tb04349.x. [DOI] [PubMed] [Google Scholar]
  39. Yuan Q. A., Jiang W. M., Krissansen G. W., Watson J. D. Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains. Int Immunol. 1990;2(11):1097–1108. doi: 10.1093/intimm/2.11.1097. [DOI] [PubMed] [Google Scholar]

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