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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 Jan 1;177(1):207–212. doi: 10.1084/jem.177.1.207

Very late antigen 4-dependent adhesion and costimulation of resting human T cells by the bacterial beta 1 integrin ligand invasin

PMCID: PMC2190859  PMID: 8418202

Abstract

Bacteria and viruses often use the normal biological properties of host adhesion molecules to infect relevant host cells. The outer membrane bacterial protein invasin mediates the attachment of Yersinia pseudotuberculosis to human cells. In vitro studies have shown that four members of the very late antigen (VLA) integrin family of adhesion molecules, VLA-3, VLA-4, VLA-5, and VLA-6, can bind to invasin. Since CD4+ T cells express and use these integrins, we have investigated the interaction of CD4+ T cells with purified invasin. Although VLA integrin-mediated adhesion of T cells to other ligands such as fibronectin does not occur at high levels unless the T cells are activated, resting T cells bind strongly to purified invasin. The binding of resting T cells to invasin requires metabolic activity and an intact cytoskeleton. Although CD4+ T cells express VLA-3, VLA-4, VLA- 5, and VLA-6, monoclonal antibody (mAb) blocking studies implicate only VLA-4 as a T cell invasin receptor. Like other integrin ligands, invasin can facilitate T cell proliferative responses induced by a CD3- specific mAb. These results suggest that the nature of the integrin ligand is a critical additional factor that regulates T cell integrin activity, and that direct interactions of T cells with bacterial pathogens such as Yersinia may be relevant to host immune responses to bacterial infection.

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Selected References

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  1. Arroyo A. G., Sánchez-Mateos P., Campanero M. R., Martín-Padura I., Dejana E., Sánchez-Madrid F. Regulation of the VLA integrin-ligand interactions through the beta 1 subunit. J Cell Biol. 1992 May;117(3):659–670. doi: 10.1083/jcb.117.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Autenrieth I. B., Tingle A., Reske-Kunz A., Heesemann J. T lymphocytes mediate protection against Yersinia enterocolitica in mice: characterization of murine T-cell clones specific for Y. enterocolitica. Infect Immun. 1992 Mar;60(3):1140–1149. doi: 10.1128/iai.60.3.1140-1149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campanero M. R., Pulido R., Ursa M. A., Rodríguez-Moya M., de Landázuri M. O., Sánchez-Madrid F. An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1-independent, triggered through the human VLA-4 integrin. J Cell Biol. 1990 Jun;110(6):2157–2165. doi: 10.1083/jcb.110.6.2157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis L. S., Oppenheimer-Marks N., Bednarczyk J. L., McIntyre B. W., Lipsky P. E. Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules. J Immunol. 1990 Aug 1;145(3):785–793. [PubMed] [Google Scholar]
  5. Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
  6. Elices M. J., Hemler M. E. The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9906–9910. doi: 10.1073/pnas.86.24.9906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Falkow S. Bacterial entry into eukaryotic cells. Cell. 1991 Jun 28;65(7):1099–1102. doi: 10.1016/0092-8674(91)90003-h. [DOI] [PubMed] [Google Scholar]
  8. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  9. Horwitz A., Duggan K., Buck C., Beckerle M. C., Burridge K. Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage. Nature. 1986 Apr 10;320(6062):531–533. doi: 10.1038/320531a0. [DOI] [PubMed] [Google Scholar]
  10. Isberg R. R. Discrimination between intracellular uptake and surface adhesion of bacterial pathogens. Science. 1991 May 17;252(5008):934–938. doi: 10.1126/science.1674624. [DOI] [PubMed] [Google Scholar]
  11. Isberg R. R., Leong J. M. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell. 1990 Mar 9;60(5):861–871. doi: 10.1016/0092-8674(90)90099-z. [DOI] [PubMed] [Google Scholar]
  12. Leong J. M., Fournier R. S., Isberg R. R. Identification of the integrin binding domain of the Yersinia pseudotuberculosis invasin protein. EMBO J. 1990 Jun;9(6):1979–1989. doi: 10.1002/j.1460-2075.1990.tb08326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matsuyama T., Yamada A., Kay J., Yamada K. M., Akiyama S. K., Schlossman S. F., Morimoto C. Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex. J Exp Med. 1989 Oct 1;170(4):1133–1148. doi: 10.1084/jem.170.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McIntyre B. W., Evans E. L., Bednarczyk J. L. Lymphocyte surface antigen L25 is a member of the integrin receptor superfamily. J Biol Chem. 1989 Aug 15;264(23):13745–13750. [PubMed] [Google Scholar]
  15. Pulido R., Elices M. J., Campanero M. R., Osborn L., Schiffer S., García-Pardo A., Lobb R., Hemler M. E., Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. J Biol Chem. 1991 Jun 5;266(16):10241–10245. [PubMed] [Google Scholar]
  16. Shimizu Y., Shaw S. Lymphocyte interactions with extracellular matrix. FASEB J. 1991 Jun;5(9):2292–2299. doi: 10.1096/fasebj.5.9.1860621. [DOI] [PubMed] [Google Scholar]
  17. Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
  18. Shimizu Y., van Seventer G. A., Ennis E., Newman W., Horgan K. J., Shaw S. Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion. J Exp Med. 1992 Feb 1;175(2):577–582. doi: 10.1084/jem.175.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol. 1990 Jul 1;145(1):59–67. [PubMed] [Google Scholar]
  20. Sonnenberg A., Modderman P. W., Hogervorst F. Laminin receptor on platelets is the integrin VLA-6. Nature. 1988 Dec 1;336(6198):487–489. doi: 10.1038/336487a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Tanaka Y., Albelda S. M., Horgan K. J., van Seventer G. A., Shimizu Y., Newman W., Hallam J., Newman P. J., Buck C. A., Shaw S. CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion. J Exp Med. 1992 Jul 1;176(1):245–253. doi: 10.1084/jem.176.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Une T. Studies on the pathogenicity of Yersinia enterocolitica. III. Comparative studies between Y. enterocolitica and Y. pseudotuberculosis. Microbiol Immunol. 1977;21(9):505–516. doi: 10.1111/j.1348-0421.1977.tb00316.x. [DOI] [PubMed] [Google Scholar]
  24. van Kooyk Y., van de Wiel-van Kemenade P., Weder P., Kuijpers T. W., Figdor C. G. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature. 1989 Dec 14;342(6251):811–813. doi: 10.1038/342811a0. [DOI] [PubMed] [Google Scholar]
  25. van Seventer G. A., Newman W., Shimizu Y., Nutman T. B., Tanaka Y., Horgan K. J., Gopal T. V., Ennis E., O'Sullivan D., Grey H. Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med. 1991 Oct 1;174(4):901–913. doi: 10.1084/jem.174.4.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van de Wiel-van Kemenade E., van Kooyk Y., de Boer A. J., Huijbens R. J., Weder P., van de Kasteele W., Melief C. J., Figdor C. G. Adhesion of T and B lymphocytes to extracellular matrix and endothelial cells can be regulated through the beta subunit of VLA. J Cell Biol. 1992 Apr;117(2):461–470. doi: 10.1083/jcb.117.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]

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