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. 1996 Mar 1;183(3):1193–1203. doi: 10.1084/jem.183.3.1193

Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin

PMCID: PMC2192327  PMID: 8642261

Abstract

We have compared the ability of human alpha/beta and gamma/delta T lymphocytes to adhere to selectin-bearing substrates, an interaction thought to be essential for homing and localization at sites of inflammation. Both T cell populations form rolling adhesions on E- and P-selectin substrates under physiologic flow conditions. Although equivalent to alpha/beta T cells in binding to E-selectin, gamma/delta T cells demonstrated greater ability to adhere to P-selectin that was purified or expressed on the surface of activated, adherent platelets. Under static conditions, 80% of gamma/delta T cells and 53% of alpha/beta T cells formed shear-resistant adhesions to P-selectin, whereas only 30% of gamma/delta and alpha/beta T cells adhered to E- selectin. The enhance ability of gamma/delta T cells to adhere to P- selectin cannot be attributed to differences in expression of the P- selectin glycoprotein ligand (PSGL-1), as all alpha/beta T cells versus approximately 75% of gamma/delta T cells expressed PSGL-1. Both cell populations expressed a similar percentage of the carbohydrate antigens sialyl LewisX and cutaneous lymphocyte-associated antigen. Depletion of lymphocyte populations or T cell clones bearing these oligosaccharides with the monoclonal antibody CSLEX-1 and HECA-452, respectively, resulted in a substantial reduction in adhesion to E-selectin and slight reduction in adhesion to P-selectin under flow conditions. Treatment of cells with an endopeptidase that selectively degrades O- sialomucins such as PSGL-1, abolished P-selectin but not E-selectin adhesion. Removal of terminal sialic acids with neuraminidase or protease treatment of cells abrogated cell adhesion to both selectin substrates. These results provide direct evidence for the presence of distinct E- and P-selectin ligands on T lymphocytes and suggest that gamma/delta T cells may be preferentially recruited to inflammatory sites during the early stages of an immune response when P-selectin is upregulated.

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Selected References

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  1. Abts H., Emmerich M., Miltenyi S., Radbruch A., Tesch H. CD20 positive human B lymphocytes separated with the magnetic cell sorter (MACS) can be induced to proliferation and antibody secretion in vitro. J Immunol Methods. 1989 Dec 20;125(1-2):19–28. doi: 10.1016/0022-1759(89)90073-2. [DOI] [PubMed] [Google Scholar]
  2. Alon R., Rossiter H., Wang X., Springer T. A., Kupper T. S. Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow. J Cell Biol. 1994 Dec;127(5):1485–1495. doi: 10.1083/jcb.127.5.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
  4. Berg E. L., Yoshino T., Rott L. S., Robinson M. K., Warnock R. A., Kishimoto T. K., Picker L. J., Butcher E. C. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991 Dec 1;174(6):1461–1466. doi: 10.1084/jem.174.6.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brennan F. M., Londei M., Jackson A. M., Hercend T., Brenner M. B., Maini R. N., Feldmann M. T cells expressing gamma delta chain receptors in rheumatoid arthritis. J Autoimmun. 1988 Aug;1(4):319–326. doi: 10.1016/0896-8411(88)90002-9. [DOI] [PubMed] [Google Scholar]
  6. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  7. Damle N. K., Klussman K., Dietsch M. T., Mohagheghpour N., Aruffo A. GMP-140 (P-selectin/CD62) binds to chronically stimulated but not resting CD4+ T lymphocytes and regulates their production of proinflammatory cytokines. Eur J Immunol. 1992 Jul;22(7):1789–1793. doi: 10.1002/eji.1830220718. [DOI] [PubMed] [Google Scholar]
  8. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  9. Devergne O., Marfaing-Koka A., Schall T. J., Leger-Ravet M. B., Sadick M., Peuchmaur M., Crevon M. C., Kim K. J., Schall T. T., Kim T. Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells. J Exp Med. 1994 May 1;179(5):1689–1694. doi: 10.1084/jem.179.5.1689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Diacovo T. G., deFougerolles A. R., Bainton D. F., Springer T. A. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J Clin Invest. 1994 Sep;94(3):1243–1251. doi: 10.1172/JCI117442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Fukushima K., Hirota M., Terasaki P. I., Wakisaka A., Togashi H., Chia D., Suyama N., Fukushi Y., Nudelman E., Hakomori S. Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res. 1984 Nov;44(11):5279–5285. [PubMed] [Google Scholar]
  13. Germain R. N., Margulies D. H. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi: 10.1146/annurev.iy.11.040193.002155. [DOI] [PubMed] [Google Scholar]
  14. Goodman T., Lefrançois L. Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature. 1988 Jun 30;333(6176):855–858. doi: 10.1038/333855a0. [DOI] [PubMed] [Google Scholar]
  15. Grober J. S., Bowen B. L., Ebling H., Athey B., Thompson C. B., Fox D. A., Stoolman L. M. Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions. J Clin Invest. 1993 Jun;91(6):2609–2619. doi: 10.1172/JCI116500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Groh V., Porcelli S., Fabbi M., Lanier L. L., Picker L. J., Anderson T., Warnke R. A., Bhan A. K., Strominger J. L., Brenner M. B. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 1;169(4):1277–1294. doi: 10.1084/jem.169.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Halstensen T. S., Scott H., Brandtzaeg P. Intraepithelial T cells of the TcR gamma/delta+ CD8- and V delta 1/J delta 1+ phenotypes are increased in coeliac disease. Scand J Immunol. 1989 Dec;30(6):665–672. doi: 10.1111/j.1365-3083.1989.tb02474.x. [DOI] [PubMed] [Google Scholar]
  18. Jones D. A., McIntire L. V., Smith C. W., Picker L. J. A two-step adhesion cascade for T cell/endothelial cell interactions under flow conditions. J Clin Invest. 1994 Dec;94(6):2443–2450. doi: 10.1172/JCI117612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jutila M. A., Bargatze R. F., Kurk S., Warnock R. A., Ehsani N., Watson S. R., Walcheck B. Cell surface P- and E-selectin support shear-dependent rolling of bovine gamma/delta T cells. J Immunol. 1994 Nov 1;153(9):3917–3928. [PubMed] [Google Scholar]
  20. Lanier L. L., Weiss A. Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus. Nature. 1986 Nov 20;324(6094):268–270. doi: 10.1038/324268a0. [DOI] [PubMed] [Google Scholar]
  21. Larsen G. R., Sako D., Ahern T. J., Shaffer M., Erban J., Sajer S. A., Gibson R. M., Wagner D. D., Furie B. C., Furie B. P-selectin and E-selectin. Distinct but overlapping leukocyte ligand specificities. J Biol Chem. 1992 Jun 5;267(16):11104–11110. [PubMed] [Google Scholar]
  22. Lasky L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. doi: 10.1126/science.1439808. [DOI] [PubMed] [Google Scholar]
  23. Lawrence M. B., Bainton D. F., Springer T. A. Neutrophil tethering to and rolling on E-selectin are separable by requirement for L-selectin. Immunity. 1994 May;1(2):137–145. doi: 10.1016/1074-7613(94)90107-4. [DOI] [PubMed] [Google Scholar]
  24. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  25. Lawrence M. B., Springer T. A. Neutrophils roll on E-selectin. J Immunol. 1993 Dec 1;151(11):6338–6346. [PubMed] [Google Scholar]
  26. Levinovitz A., Mühlhoff J., Isenmann S., Vestweber D. Identification of a glycoprotein ligand for E-selectin on mouse myeloid cells. J Cell Biol. 1993 Apr;121(2):449–459. doi: 10.1083/jcb.121.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lobb R. R., Chi-Rosso G., Leone D. R., Rosa M. D., Bixler S., Newman B. M., Luhowskyj S., Benjamin C. D., Dougas I. G., Goelz S. E. Expression and functional characterization of a soluble form of endothelial-leukocyte adhesion molecule 1. J Immunol. 1991 Jul 1;147(1):124–129. [PubMed] [Google Scholar]
  28. McEver R. P., Martin M. N. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem. 1984 Aug 10;259(15):9799–9804. [PubMed] [Google Scholar]
  29. Meliconi R., Pitzalis C., Kingsley G. H., Panayi G. S. Gamma/delta T cells and their subpopulations in blood and synovial fluid from rheumatoid arthritis and spondyloarthritis. Clin Immunol Immunopathol. 1991 Apr;59(1):165–172. doi: 10.1016/0090-1229(91)90090-w. [DOI] [PubMed] [Google Scholar]
  30. Miller L. J., Bainton D. F., Borregaard N., Springer T. A. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest. 1987 Aug;80(2):535–544. doi: 10.1172/JCI113102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
  32. Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
  33. Moore K. L., Eaton S. F., Lyons D. E., Lichenstein H. S., Cummings R. D., McEver R. P. The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine. J Biol Chem. 1994 Sep 16;269(37):23318–23327. [PubMed] [Google Scholar]
  34. Moore K. L., Patel K. D., Bruehl R. E., Li F., Johnson D. A., Lichenstein H. S., Cummings R. D., Bainton D. F., McEver R. P. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol. 1995 Feb;128(4):661–671. doi: 10.1083/jcb.128.4.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Moore K. L., Thompson L. F. P-selectin (CD62) binds to subpopulations of human memory T lymphocytes and natural killer cells. Biochem Biophys Res Commun. 1992 Jul 15;186(1):173–181. doi: 10.1016/s0006-291x(05)80790-9. [DOI] [PubMed] [Google Scholar]
  36. Morita C. T., Beckman E. M., Bukowski J. F., Tanaka Y., Band H., Bloom B. R., Golan D. E., Brenner M. B. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity. 1995 Oct;3(4):495–507. doi: 10.1016/1074-7613(95)90178-7. [DOI] [PubMed] [Google Scholar]
  37. Morita C. T., Verma S., Aparicio P., Martinez C., Spits H., Brenner M. B. Functionally distinct subsets of human gamma/delta T cells. Eur J Immunol. 1991 Dec;21(12):2999–3007. doi: 10.1002/eji.1830211215. [DOI] [PubMed] [Google Scholar]
  38. Nolte D., Schmid P., Jäger U., Botzlar A., Roesken F., Hecht R., Uhl E., Messmer K., Vestweber D. Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin. Am J Physiol. 1994 Oct;267(4 Pt 2):H1637–H1642. doi: 10.1152/ajpheart.1994.267.4.H1637. [DOI] [PubMed] [Google Scholar]
  39. Norgard K. E., Moore K. L., Diaz S., Stults N. L., Ushiyama S., McEver R. P., Cummings R. D., Varki A. Characterization of a specific ligand for P-selectin on myeloid cells. A minor glycoprotein with sialylated O-linked oligosaccharides. J Biol Chem. 1993 Jun 15;268(17):12764–12774. [PubMed] [Google Scholar]
  40. Parker C. M., Groh V., Band H., Porcelli S. A., Morita C., Fabbi M., Glass D., Strominger J. L., Brenner M. B. Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J Exp Med. 1990 May 1;171(5):1597–1612. doi: 10.1084/jem.171.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Picker L. J., Treer J. R., Ferguson-Darnell B., Collins P. A., Bergstresser P. R., Terstappen L. W. Control of lymphocyte recirculation in man. II. Differential regulation of the cutaneous lymphocyte-associated antigen, a tissue-selective homing receptor for skin-homing T cells. J Immunol. 1993 Feb 1;150(3):1122–1136. [PubMed] [Google Scholar]
  43. Picker L. J., Warnock R. A., Burns A. R., Doerschuk C. M., Berg E. L., Butcher E. C. The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140. Cell. 1991 Sep 6;66(5):921–933. doi: 10.1016/0092-8674(91)90438-5. [DOI] [PubMed] [Google Scholar]
  44. Sako D., Chang X. J., Barone K. M., Vachino G., White H. M., Shaw G., Veldman G. M., Bean K. M., Ahern T. J., Furie B. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993 Dec 17;75(6):1179–1186. doi: 10.1016/0092-8674(93)90327-m. [DOI] [PubMed] [Google Scholar]
  45. Selmaj K., Brosnan C. F., Raine C. S. Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6452–6456. doi: 10.1073/pnas.88.15.6452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  47. Springer T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. 1995;57:827–872. doi: 10.1146/annurev.ph.57.030195.004143. [DOI] [PubMed] [Google Scholar]
  48. Sutherland D. R., Marsh J. C., Davidson J., Baker M. A., Keating A., Mellors A. Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica glycoprotease: implications for purification of CD34-positive progenitor cells. Exp Hematol. 1992 Jun;20(5):590–599. [PubMed] [Google Scholar]
  49. Takada A., Ohmori K., Takahashi N., Tsuyuoka K., Yago A., Zenita K., Hasegawa A., Kannagi R. Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun. 1991 Sep 16;179(2):713–719. doi: 10.1016/0006-291x(91)91875-d. [DOI] [PubMed] [Google Scholar]
  50. Tanaka Y., Morita C. T., Tanaka Y., Nieves E., Brenner M. B., Bloom B. R. Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. Nature. 1995 May 11;375(6527):155–158. doi: 10.1038/375155a0. [DOI] [PubMed] [Google Scholar]
  51. Vachino G., Chang X. J., Veldman G. M., Kumar R., Sako D., Fouser L. A., Berndt M. C., Cumming D. A. P-selectin glycoprotein ligand-1 is the major counter-receptor for P-selectin on stimulated T cells and is widely distributed in non-functional form on many lymphocytic cells. J Biol Chem. 1995 Sep 15;270(37):21966–21974. doi: 10.1074/jbc.270.37.21966. [DOI] [PubMed] [Google Scholar]
  52. Walcheck B., Watts G., Jutila M. A. Bovine gamma/delta T cells bind E-selectin via a novel glycoprotein receptor: first characterization of a lymphocyte/E-selectin interaction in an animal model. J Exp Med. 1993 Sep 1;178(3):853–863. doi: 10.1084/jem.178.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wucherpfennig K. W., Newcombe J., Li H., Keddy C., Cuzner M. L., Hafler D. A. Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4588–4592. doi: 10.1073/pnas.89.10.4588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Yewdell J. W., Bennink J. R. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv Immunol. 1992;52:1–123. doi: 10.1016/s0065-2776(08)60875-5. [DOI] [PubMed] [Google Scholar]
  55. de Bruijne-Admiraal L. G., Modderman P. W., Von dem Borne A. E., Sonnenberg A. P-selectin mediates Ca(2+)-dependent adhesion of activated platelets to many different types of leukocytes: detection by flow cytometry. Blood. 1992 Jul 1;80(1):134–142. [PubMed] [Google Scholar]

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