Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Nov;145(5):1148–1158.

Expression of monoclonal antibody HML-1-defined alpha E beta 7 integrin in cutaneous T cell lymphoma.

I Simonitsch 1, B Volc-Platzer 1, I Mosberger 1, T Radaszkiewicz 1
PMCID: PMC1887437  PMID: 7977645

Abstract

Considering that integrins may play a major role in the localization in distinct biological features as well as in the dissemination of several types of lymphomas, we studied the expression of the monoclonal antibody HML-1-defined alpha E beta 7 integrin (CD103) in the clinically and histologically determined stages of 53 mycosis fungoides (MF) skin biopsies and in 16 affected lymph nodes. Immunoperoxidase staining revealed HML-1 immunoreactivity with T cells in the early stages of disease (patch and plaque stage MF). HML-1 expression was more pronounced on infiltrating epidermal than on dermal T cells. In contrast to early stages, tumor stage MF and lymph nodes affected in the course of cutaneous T cell lymphoma were HML-1 negative. We found a strong association between HML-1 expression, epidermotropism of infiltrating T cells, and the stage of disease. We provide evidence that: 1) the loss of the HML-1 antigen on T cells in MF is a marker of poor prognosis and 2) because the HML-1 antigen is selectively expressed on T lymphocytes of epithelial sites such as gut and skin, our results are compatible with the view that alpha E beta 7 integrins perform homing receptor functions for epitheliotropic T cells.

Full text

PDF
1148

Images in this article

1151Figure 1
on p.1151
1152Figure 3
on p.1152
1153Figure 4
on p.1153
1153Figure 5
on p.1153
1154Figure 6
on p.1154
1154Figure 7
on p.1154
1155Figure 8
on p.1155

Selected References

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

  1. Abel E. A., Wood G. S., Hoppe R. T., Warnke R. A. Expression of Leu-8 antigen, a majority T-cell marker, is uncommon in mycosis fungoides. J Invest Dermatol. 1985 Sep;85(3):199–202. doi: 10.1111/1523-1747.ep12276668. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Brousse N., Jarry A., Peuchmaur M., Gaulard P., D'Agay M. F., Guy-Grand D., Cerf-Bensussan N. Monoclonal antibody (HML-1) reactivity of T-cell lymphomas. Lancet. 1989 Nov 4;2(8671):1107–1108. doi: 10.1016/s0140-6736(89)91130-6. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Cerf-Bensussan N., Jarry A., Gnéragbé T., Brousse N., Lisowska-Grospierre B., Griscelli C., Guy-Grand D. Monoclonal antibodies specific for intestinal lymphocytes. Monogr Allergy. 1988;24:167–172. [PubMed] [Google Scholar]
  8. Chott A., Dragosics B., Radaszkiewicz T. Peripheral T-cell lymphomas of the intestine. Am J Pathol. 1992 Dec;141(6):1361–1371. [PMC free article] [PubMed] [Google Scholar]
  9. Coombe D. R., Rider C. C. Lymphocyte homing receptors cloned--a role for anionic polysaccharides in lymphocyte adhesion. Immunol Today. 1989 Sep;10(9):289–291. doi: 10.1016/0167-5699(89)90083-2. [DOI] [PubMed] [Google Scholar]
  10. Duijvestijn A. M., Horst E., Pals S. T., Rouse B. N., Steere A. C., Picker L. J., Meijer C. J., Butcher E. C. High endothelial differentiation in human lymphoid and inflammatory tissues defined by monoclonal antibody HECA-452. Am J Pathol. 1988 Jan;130(1):147–155. [PMC free article] [PubMed] [Google Scholar]
  11. Flenghi L., Spinozzi F., Stein H., Krushwitz M., Pileri S., Falini B. LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia. Br J Haematol. 1990 Dec;76(4):451–459. doi: 10.1111/j.1365-2141.1990.tb07900.x. [DOI] [PubMed] [Google Scholar]
  12. Gatenby P. A., Kansas G. S., Xian C. Y., Evans R. L., Engleman E. G. Dissection of immunoregulatory subpopulations of T lymphocytes within the helper and suppressor sublineages in man. J Immunol. 1982 Nov;129(5):1997–2000. [PubMed] [Google Scholar]
  13. Hastrup N., Ralfkiaer E., Pallesen G. Aberrant phenotypes in peripheral T cell lymphomas. J Clin Pathol. 1989 Apr;42(4):398–402. doi: 10.1136/jcp.42.4.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hogg N. Roll, roll, roll your leucocyte gently down the vein.... Immunol Today. 1992 Apr;13(4):113–115. doi: 10.1016/0167-5699(92)90103-E. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  17. Jalkanen S., Reichert R. A., Gallatin W. M., Bargatze R. F., Weissman I. L., Butcher E. C. Homing receptors and the control of lymphocyte migration. Immunol Rev. 1986 Jun;91:39–60. doi: 10.1111/j.1600-065x.1986.tb01483.x. [DOI] [PubMed] [Google Scholar]
  18. Kernohan N. M., Smart L. M. Anomalous phenotype of cutaneous T-cell infiltrates. J Pathol. 1990 Jan;160(1):81–82. doi: 10.1002/path.1711600116. [DOI] [PubMed] [Google Scholar]
  19. Kilshaw P. J., Murant S. J. A new surface antigen on intraepithelial lymphocytes in the intestine. Eur J Immunol. 1990 Oct;20(10):2201–2207. doi: 10.1002/eji.1830201008. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Kruschwitz M., Fritzsche G., Schwarting R., Micklem K., Mason D. Y., Falini B., Stein H. Ber-ACT8: new monoclonal antibody to the mucosa lymphocyte antigen. J Clin Pathol. 1991 Aug;44(8):636–645. doi: 10.1136/jcp.44.8.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lefrançois L., Barrett T. A., Havran W. L., Puddington L. Developmental expression of the alpha IEL beta 7 integrin on T cell receptor gamma delta and T cell receptor alpha beta T cells. Eur J Immunol. 1994 Mar;24(3):635–640. doi: 10.1002/eji.1830240322. [DOI] [PubMed] [Google Scholar]
  23. Mason D. Y., Sammons R. Alkaline phosphatase and peroxidase for double immunoenzymatic labelling of cellular constituents. J Clin Pathol. 1978 May;31(5):454–460. doi: 10.1136/jcp.31.5.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Michl J., Qiu Q. Y., Kuerer H. M. Homing receptors and addressins. Curr Opin Immunol. 1991 Jun;3(3):373–382. doi: 10.1016/0952-7915(91)90040-8. [DOI] [PubMed] [Google Scholar]
  25. Micklem K. J., Dong Y., Willis A., Pulford K. A., Visser L., Dürkop H., Poppema S., Stein H., Mason D. Y. HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit. Am J Pathol. 1991 Dec;139(6):1297–1301. [PMC free article] [PubMed] [Google Scholar]
  26. Monoclonal antibody (HML-1) labelling of T-cell lymphomas. Lancet. 1989 Jan 28;1(8631):223–224. [PubMed] [Google Scholar]
  27. Möller P., Mielke B., Moldenhauer G. Monoclonal antibody HML-1, a marker for intraepithelial T cells and lymphomas derived thereof, also recognizes hairy cell leukemia and some B-cell lymphomas. Am J Pathol. 1990 Mar;136(3):509–512. [PMC free article] [PubMed] [Google Scholar]
  28. Noorduyn L. A., Beljaards R. C., Pals S. T., van Heerde P., Radaszkiewicz T., Willemze R., Meijer C. J. Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas. Histopathology. 1992 Jul;21(1):59–64. doi: 10.1111/j.1365-2559.1992.tb00343.x. [DOI] [PubMed] [Google Scholar]
  29. Pals S. T., Meijer C. J., Radaszkiewicz T. Expression of the human peripheral lymph node homing receptor (LECAM-1) in nodal and gastrointestinal non-Hodgkin's lymphomas. Leukemia. 1991 Jul;5(7):628–631. [PubMed] [Google Scholar]
  30. Picker L. J., Michie S. A., Rott L. S., Butcher E. C. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990 May;136(5):1053–1068. [PMC free article] [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. Schwarting R., Dienemann D., Kruschwitz M., Fritsche G., Stein H. Specificities of monoclonal antibodies B-ly7 and HML-1 are identical. Blood. 1990 Jan 1;75(1):320–321. [PubMed] [Google Scholar]
  33. 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]
  34. Spencer J., Cerf-Bensussan N., Jarry A., Brousse N., Guy-Grand D., Krajewski A. S., Isaacson P. G. Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol. 1988 Jul;132(1):1–5. [PMC free article] [PubMed] [Google Scholar]
  35. Sperling M., Kaudewitz P., Braun-Falco O., Stein H. Reactivity of T cells in mycosis fungoides exhibiting marked epidermotropism with the monoclonal antibody HML-1 that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol. 1989 May;134(5):955–960. [PMC free article] [PubMed] [Google Scholar]
  36. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  37. Stein H., Dienemann D., Sperling M., Zeitz M., Riecken E. O. Identification of a T cell lymphoma category derived from intestinal-mucosa-associated T cells. Lancet. 1988 Nov 5;2(8619):1053–1054. doi: 10.1016/S0140-6736(88)90068-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stein H., Gerdes J., Schwab U., Lemke H., Mason D. Y., Ziegler A., Schienle W., Diehl V. Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population. Int J Cancer. 1982 Oct 15;30(4):445–459. doi: 10.1002/ijc.2910300411. [DOI] [PubMed] [Google Scholar]
  39. Sterry W., Mielke V., Konter U., Kellner I., Boehncke W. H. Role of beta 1-integrins in epidermotropism of malignant T cells. Am J Pathol. 1992 Oct;141(4):855–860. [PMC free article] [PubMed] [Google Scholar]
  40. Sterry W. Mycosis fungoides. Curr Top Pathol. 1985;74:167–223. doi: 10.1007/978-3-642-69574-2_5. [DOI] [PubMed] [Google Scholar]
  41. Suchi T., Lennert K., Tu L. Y., Kikuchi M., Sato E., Stansfeld A. G., Feller A. C. Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification. J Clin Pathol. 1987 Sep;40(9):995–1015. doi: 10.1136/jcp.40.9.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Visser L., Shaw A., Slupsky J., Vos H., Poppema S. Monoclonal antibodies reactive with hairy cell leukemia. Blood. 1989 Jul;74(1):320–325. [PubMed] [Google Scholar]
  43. Wood G. S., Abel E. A., Hoppe R. T., Warnke R. A. Leu-8 and Leu-9 antigen phenotypes: immunologic criteria for the distinction of mycosis fungoides from cutaneous inflammation. J Am Acad Dermatol. 1986 Jun;14(6):1006–1013. doi: 10.1016/s0190-9622(86)70124-2. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES