The Level of CD26 Determines the Rate of HIV Entry in a CD4+ T-Cell Line

  • Christian Callebaut
  • Etienne Jacotot
  • Julià Blanco
  • Bernard Krust
  • Ara G. Hovanessian
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 421)


We have reported that CD26 could serve as a cofactor of CD4 in HIV entry. Recently, more evidence has been provided for the implication of CD26 in HIV entry, replication and cytopathic effect. Along with, we have demonstrated that the level of CD26 may determine the rate of HIV-envelope induced-apoptosis. The role of CD26 in HIV entry was further investigated using CEM T-cell line. Clones were established by transfection, expressing different levels of CD26. Entry, infection and cytopathic effect were monitored in several independent clones, and were found to be delayed in clones CD26Low and CD26-SuperHigh compared to clones CD26-High. The delay was most significant in clones CD26-AntiSense, without any apparent cytopathic effect. These results demonstrate that relatively enhanced levels of CD26 contribute to an increased virus infection. Furthermore, they illustrate that CD26-SuperHigh clones manifest a phenotype similar to CD26-Low clones. This point out the critical role of CD26 in the rate of HIV entry and its cytopathic effect, two events which are initiated by the interaction of HIV envelope glycoproteins with cell-surface CD4.


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Cytopathic Effect Adenosine Deaminase Purinenucleoside Phosphorylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fleischer, B, CD26: a surface protease involved in T-cell activation. Immunol Today, 1994. 15 (4): p. 180–4.PubMedCrossRefGoogle Scholar
  2. Callebaut, C, et al., T cell activation antigen. CD26. as a cofactor for entry of HIV in CD4+ cells. Science, 1993. 262(5142): p. 2045–50.Google Scholar
  3. 3.
    Callebaut, C, et al., Entry of HII“ into CD4+ cells requires the T-cell activation antigen CD26/DPP /V in V/HL’ Colloque des Ceni Gardes,M. Girard and B. Dodet, Editors. 1993b, In Retrovirus of Human AIDS and related diseases: p. 187–193.Google Scholar
  4. Broder, CC, et al., CD26 antigen and HIV fusion? [letter: comment]. Science, 1994. 264(5162): p. 1156–9.Google Scholar
  5. 5.
    Patience, C, et al., CD26 antigen and HIV fusion? [letter; commuent]. Science, 1994. 264(5162): p. II59–60.Google Scholar
  6. 6.
    Camerini, D, Planelles, V, and Chen, IS, CD26 antigen and HIV fusion? [letter: comment]. Science, 1994. 264(5162): p. 1160`1.Google Scholar
  7. 7.
    Alison, M and Dragic, T, (’D26 antigen and HIV fission? [letter: comment] Science, 1994. 264 (5162): p. 1161–2.CrossRefGoogle Scholar
  8. Callebaut, C, et al., CD26 antigen and HIV fusion? [Response]. Science, 1994. 264(20 May 1994): p. 1156–1165.Google Scholar
  9. Oravecz, T, et al., CD26 expression correlates with entry, replication and cpropathiciir of nonocytonapic HIV-1 strains in a T-cell line face comments]. Nat Med, 1995. 1(9): p. 919–26.Google Scholar
  10. 10.
    Callebaut, C and Hovanessian, AG, CD26 and HIV infection. Res. Virol., 1996. 147: p. 67 fig.Google Scholar
  11. Chin, LT, et al., Molecular characterization of a human anti-HIV I monoclonal antibody revealed a CD26- related motif in CDR2. Immunology Letters, 1995. 44: p. 25–30.Google Scholar
  12. 12.
    Callebaut, C, et al., The role of CD26 in HIV infection: viral entry and its cytopathic effect. in /Xi Colloquy des Cent Gardes,M. Girard and B. Dodet. Editors. 19946, In Rétrovirus of Human AIDS and related diseases: p. 141–149.Google Scholar
  13. 13.
    Jacotot, E, et al_ HIV envelope-ghroproteins induced cell-killing by apoptosis is enhanced frith increased expression of CD26 in (’D4’ T cells Virology, 1996. 223: p. 318–330.Google Scholar
  14. Moore, JP, et al., The H1V-cell fusion reaction. in Viral Fusion Mechanisms. J. Bentz. Editor. 1993, p. 233–289.Google Scholar
  15. 15.
    Laurent-Crawford, AG, ei cul., Membrane expression of HIV envelope glvcoproiein.s triggers apoptosis in CD4 cells. Aids Res Hum Retroviruses, 1993. 9 (8): p. 761–73.Google Scholar
  16. 16.
    Maddon, PJ, et al., The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986. 47: p. 333–348.PubMedCrossRefGoogle Scholar
  17. 17.
    Sattentau, Q.1 and Moore, JP, Conformational changes induced in the human immunodeficiency vino. envelope glvroprotein by soluble CD4 binding. J Exp Med, 1991. 174 (2): p. 407–15.CrossRefGoogle Scholar
  18. Schulz, TF, et al., Effect ofnrutations in the V3 loop of HIV-1 gp120 on infectivity and susceptibility to proteolytic cleavage. Aids Res Hum Retroviruses, 1993. 9(2): p. I5966.Google Scholar
  19. 19.
    Dragic, T, Picard. L, and Alison, M, Proteinase-resistant factors in human erythrocyte membranes mediate CD4-dependent fusion with cells evpres.sing human tnuntnodeficiency virus type I envelopeghroproteins. J Virol, 1995. 69 (2): p. 1013–8.PubMedGoogle Scholar
  20. Feng, Y, et al., HIV -1 entry cofactor: functional cDNA cloning of a seven-transmembrmue, G protein-coupled receptor [see comments]. Science, 1996. 272(5263): p. 872–7.Google Scholar
  21. Dragic, T, et al., HI V I entry into CD4+ cells is mediated by the chenokine receptor CC-CKR-5. Nature. 1996. 381: p. 667–673.Google Scholar
  22. Jacotot, E, et al., CD26 as positive regulator of HIV envelope-glvcoproteins induced apoptosis in CD4’ T cells,in Cellular Peptidases in Immune Functions and Diseases,S. Ansorge and J. Langner, Editors. Plenum: 1997, p. 207–216.Google Scholar
  23. Valenzuela, A, et al., HIV I envelope gp120 and viral particles block adenosine deaminase binding to ho-nut!? CD26. in Cellular Peptidases in Immune Functions and Diseases,S. Ansorge and J. Langner, Editors. Plenum: 1997, p. 185–192.Google Scholar
  24. Pantaleo, G, et al., Dissociation between syncytia formation and HIV.spreading. Suppression of syncytia formation does not necessarily reflect inhibition of HIV infection. Eur. J. Immunol., 1991. 21: p. 1771–1774.Google Scholar
  25. Tanaka, T, et al., Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidtl peptidose IV Proc Natl Acad Sci U S A, 1994. 91(8): p. 3082–6.Google Scholar
  26. Kameoka, J, et al., Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science, 1993. 261(5120): p. 466–9.Google Scholar
  27. 27.
    Martin, M, et al., Expression of ecto-adenosine deaminase and CD26 in human T cells triggered by the TCR-CD3 complex. Possible role of adenosine deaminase as costimulatory molecule. J Immunol, 1995. 155 (10): p. 4630–43PubMedGoogle Scholar
  28. 28.
    Dong, RP, et al., Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response. J Immunol, 1996. 156 (4): p. 1349–55.PubMedGoogle Scholar
  29. 29.
    Hershfield, MS and Mitchell, BS, Immunodeficiency diseases caused by adenosine deaminase deficiency and purinenucleoside phosphorylase deficiency, in The Metabolic and Molecular Bases of Inherited Disease, S. C.R., et al., Editors. 1995, p. 1745–1768.Google Scholar
  30. 30.
    Mentlein, R, et al., Influence of pregnancy on dipeptidyl peptidase IV activity (CD 26 leukocyte differentiation antigen) of circulating lymphocytes. Eur J Clin Chem Clin Biochem, 1991. 29 (8): p. 477–80.PubMedGoogle Scholar
  31. 31.
    Rich, KC, et al., CD4+ lymphocytes in perinatal human immunodeficiency virus (HIV) infection: evidence for pregnancy-induced immune depression in uninfected and HIV-infected women. J Infect Dis, 1995. 172 (5): p. 1221–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Graziosi, C, et al., HIV-1 infection in the lymphoid organs. Aids, 1993. 7 (2): p. S53–8.Google Scholar
  33. 33.
    Gougeon, M-L, et al., Selective loss of CD4+/CD26+ T cell subset during HIV infection. Res. Immunol, 1996. 147, 5–8.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Christian Callebaut
    • 1
  • Etienne Jacotot
    • 1
  • Julià Blanco
    • 1
  • Bernard Krust
    • 1
  • Ara G. Hovanessian
    • 1
  1. 1.Unité de Virologie et Immunologie Cellulaire Unité Associée CNRS 1157 Département Retrovirus-SIDAInstitut PasteurParis cedex 15France

Personalised recommendations