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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Mar 15;97(6):1545–1549. doi: 10.1172/JCI118577

Potentiation of the immune response in HIV-1+ individuals.

T Schmitz 1, R Underwood 1, R Khiroya 1, W W Bachovchin 1, B T Huber 1
PMCID: PMC507215  PMID: 8617888

Abstract

T cells from HIV-1+ individuals have a defect in mounting an antigen specific response. HIV-1 Tat has been implicated as the causative agent of this immunosuppression. We have previously shown that HIV-1 Tat inhibits antigen specific proliferation of normal T cells in vitro by binding to the accessory molecule CD26, a dipeptidase expressed on the surface of activated T cells. We now demonstrate that the defective in vitro recall antigen response in HIV-1 infected individuals can be restored by the addition of soluble CD26, probably by serving as a decoy receptor for HIV-1 Tat. The restored response is comparable to that of an HIV-1- individual, suggesting that early in HIV infection there is a block in the memory cell response, rather than deletion of these cells.

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Selected References

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  1. Blazquez M. V., Madueño J. A., Gonzalez R., Jurado R., Bachovchin W. W., Peña J., Muñoz E. Selective decrease of CD26 expression in T cells from HIV-1-infected individuals. J Immunol. 1992 Nov 1;149(9):3073–3077. [PubMed] [Google Scholar]
  2. Chirmule N., Than S., Khan S. A., Pahwa S. Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. J Virol. 1995 Jan;69(1):492–498. doi: 10.1128/jvi.69.1.492-498.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dang N. H., Torimoto Y., Deusch K., Schlossman S. F., Morimoto C. Comitogenic effect of solid-phase immobilized anti-1F7 on human CD4 T cell activation via CD3 and CD2 pathways. J Immunol. 1990 Jun 1;144(11):4092–4100. [PubMed] [Google Scholar]
  4. Eguchi K., Ueki Y., Shimomura C., Otsubo T., Nakao H., Migita K., Kawakami A., Matsunaga M., Tezuka H., Ishikawa N. Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease. J Immunol. 1989 Jun 15;142(12):4233–4240. [PubMed] [Google Scholar]
  5. Flentke G. R., Munoz E., Huber B. T., Plaut A. G., Kettner C. A., Bachovchin W. W. Inhibition of dipeptidyl aminopeptidase IV (DP-IV) by Xaa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T-cell function. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1556–1559. doi: 10.1073/pnas.88.4.1556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fox D. A., Hussey R. E., Fitzgerald K. A., Acuto O., Poole C., Palley L., Daley J. F., Schlossman S. F., Reinherz E. L. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984 Sep;133(3):1250–1256. [PubMed] [Google Scholar]
  7. Gossrau R. Cytochemistry of membrane proteases. Histochem J. 1985 Jul;17(7):737–771. doi: 10.1007/BF01003312. [DOI] [PubMed] [Google Scholar]
  8. Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gutheil W. G., Subramanyam M., Flentke G. R., Sanford D. G., Munoz E., Huber B. T., Bachovchin W. W. Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV (CD26): a possible mechanism for Tat's immunosuppressive activity. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6594–6598. doi: 10.1073/pnas.91.14.6594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hafler D. A., Fox D. A., Manning M. E., Schlossman S. F., Reinherz E. L., Weiner H. L. In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med. 1985 May 30;312(22):1405–1411. doi: 10.1056/NEJM198505303122201. [DOI] [PubMed] [Google Scholar]
  11. Helland D. E., Welles J. L., Caputo A., Haseltine W. A. Transcellular transactivation by the human immunodeficiency virus type 1 tat protein. J Virol. 1991 Aug;65(8):4547–4549. doi: 10.1128/jvi.65.8.4547-4549.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kubota T., Flentke G. R., Bachovchin W. W., Stollar B. D. Involvement of dipeptidyl peptidase IV in an in vivo immune response. Clin Exp Immunol. 1992 Aug;89(2):192–197. doi: 10.1111/j.1365-2249.1992.tb06931.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lane H. C., Depper J. M., Greene W. C., Whalen G., Waldmann T. A., Fauci A. S. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985 Jul 11;313(2):79–84. doi: 10.1056/NEJM198507113130204. [DOI] [PubMed] [Google Scholar]
  14. Li C. J., Friedman D. J., Wang C., Metelev V., Pardee A. B. Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science. 1995 Apr 21;268(5209):429–431. doi: 10.1126/science.7716549. [DOI] [PubMed] [Google Scholar]
  15. Muscat C., Bertotto A., Agea E., Bistoni O., Ercolani R., Tognellini R., Spinozzi F., Cesarotti M., Gerli R. Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients. Clin Exp Immunol. 1994 Nov;98(2):252–256. doi: 10.1111/j.1365-2249.1994.tb06134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Püschel G., Mentlein R., Heymann E. Isolation and characterization of dipeptidyl peptidase IV from human placenta. Eur J Biochem. 1982 Aug;126(2):359–365. doi: 10.1111/j.1432-1033.1982.tb06788.x. [DOI] [PubMed] [Google Scholar]
  17. Sarin A., Clerici M., Blatt S. P., Hendrix C. W., Shearer G. M., Henkart P. A. Inhibition of activation-induced programmed cell death and restoration of defective immune responses of HIV+ donors by cysteine protease inhibitors. J Immunol. 1994 Jul 15;153(2):862–872. [PubMed] [Google Scholar]
  18. Subramanyam M., Gutheil W. G., Bachovchin W. W., Huber B. T. Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. J Immunol. 1993 Mar 15;150(6):2544–2553. [PubMed] [Google Scholar]
  19. Svensson B., Danielsen M., Staun M., Jeppesen L., Norén O., Sjöström H. An amphiphilic form of dipeptidyl peptidase IV from pig small-intestinal brush-border membrane. Purification by immunoadsorbent chromatography and some properties. Eur J Biochem. 1978 Oct 16;90(3):489–498. doi: 10.1111/j.1432-1033.1978.tb12628.x. [DOI] [PubMed] [Google Scholar]
  20. Tanaka T., Duke-Cohan J. S., Kameoka J., Yaron A., Lee I., Schlossman S. F., Morimoto C. Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3082–3086. doi: 10.1073/pnas.91.8.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vanham G., Kestens L., De Meester I., Vingerhoets J., Penne G., Vanhoof G., Scharpé S., Heyligen H., Bosmans E., Ceuppens J. L. Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects. J Acquir Immune Defic Syndr. 1993 Jul;6(7):749–757. [PubMed] [Google Scholar]
  22. Viscidi R. P., Mayur K., Lederman H. M., Frankel A. D. Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science. 1989 Dec 22;246(4937):1606–1608. doi: 10.1126/science.2556795. [DOI] [PubMed] [Google Scholar]
  23. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  24. Wolf B., Fischer G., Barth A. Kinetische Untersuchungen an der Dipeptidyl-peptidase IV. Acta Biol Med Ger. 1978;37(3):409–420. [PubMed] [Google Scholar]
  25. Yang Y., Bailey J., Vacchio M. S., Yarchoan R., Ashwell J. D. Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3051–3055. doi: 10.1073/pnas.92.7.3051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yang Y., Vacchio M. S., Ashwell J. D. 9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6170–6174. doi: 10.1073/pnas.90.13.6170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yaron A., Naider F. Proline-dependent structural and biological properties of peptides and proteins. Crit Rev Biochem Mol Biol. 1993;28(1):31–81. doi: 10.3109/10409239309082572. [DOI] [PubMed] [Google Scholar]

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