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Proc Natl Acad Sci U S A. 1994 Apr 12; 91(8): 3082–3086.

Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV.


The addition of a soluble recombinant CD26 (sCD26) enhanced proliferation of peripheral blood lymphocytes induced by the recall antigen tetanus toxoid. sCD26 itself did not provide a mitogenic signal and did not augment the proliferative response of T cells to other mitogenic stimuli such as phytohemagglutinin and anti-CD3. Dipeptidyl peptidase IV-negative sCD26 did not have this enhancement effect, implying a requirement for enzyme activity. It was found that there exists a large variation in the levels of human plasma sCD26/dipeptidyl peptidase IV in vivo which may regulate T-cell activity. Peripheral blood lymphocytes from individuals whose plasma sCD26 was high and responded strongly to tetanus toxoid stimulation were insensitive to the enhancing effects of exogenously added sCD26. This suggests that plasma sCD26 had modulated the responsiveness of T cells of these individuals in vivo and that the endogenous plasma sCD26 regulates immune responses by allowing antigen-specific T cells to exert a maximal response to their specific antigen.

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  • Morimoto C, Torimoto Y, Levinson G, Rudd CE, Schrieber M, Dang NH, Letvin NL, Schlossman SF. 1F7, a novel cell surface molecule, involved in helper function of CD4 cells. J Immunol. 1989 Dec 1;143(11):3430–3439. [PubMed]
  • Fox DA, Hussey RE, Fitzgerald KA, Acuto O, Poole C, Palley L, Daley JF, Schlossman SF, Reinherz EL. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984 Sep;133(3):1250–1256. [PubMed]
  • Torimoto Y, Dang NH, Tanaka T, Prado C, Schlossman SF, Morimoto C. Biochemical characterization of CD26 (dipeptidyl peptidase IV): functional comparison of distinct epitopes recognized by various anti-CD26 monoclonal antibodies. Mol Immunol. 1992 Feb;29(2):183–192. [PubMed]
  • Hegen M, Niedobitek G, Klein CE, Stein H, Fleischer B. The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity. J Immunol. 1990 Apr 15;144(8):2908–2914. [PubMed]
  • Kenny AJ, Booth AG, George SG, Ingram J, Kershaw D, Wood EJ, Young AR. Dipeptidyl peptidase IV, a kidney brush-border serine peptidase. Biochem J. 1976 Jul 1;157(1):169–182. [PMC free article] [PubMed]
  • Dang NH, Torimoto Y, Deusch K, Schlossman SF, 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]
  • Dang NH, Torimoto Y, Schlossman SF, Morimoto C. Human CD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family. J Exp Med. 1990 Aug 1;172(2):649–652. [PMC free article] [PubMed]
  • Fleischer B, Sturm E, De Vries JE, Spits H. Triggering of cytotoxic T lymphocytes and NK cells via the Tp103 pathway is dependent on the expression of the T cell receptor/CD3 complex. J Immunol. 1988 Aug 15;141(4):1103–1107. [PubMed]
  • Flentke GR, Munoz E, Huber BT, Plaut AG, Kettner CA, Bachovchin WW. 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. [PMC free article] [PubMed]
  • Tanaka T, Camerini D, Seed B, Torimoto Y, Dang NH, Kameoka J, Dahlberg HN, Schlossman SF, Morimoto C. Cloning and functional expression of the T cell activation antigen CD26. J Immunol. 1992 Jul 15;149(2):481–486. [PubMed]
  • Torimoto Y, Dang NH, Vivier E, Tanaka T, Schlossman SF, Morimoto C. Coassociation of CD26 (dipeptidyl peptidase IV) with CD45 on the surface of human T lymphocytes. J Immunol. 1991 Oct 15;147(8):2514–2517. [PubMed]
  • Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993 Jul 23;261(5120):466–469. [PubMed]
  • Tanaka T, Kameoka J, Yaron A, Schlossman SF, Morimoto C. The costimulatory activity of the CD26 antigen requires dipeptidyl peptidase IV enzymatic activity. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4586–4590. [PMC free article] [PubMed]
  • Kaufman RJ, Davies MV, Pathak VK, Hershey JW. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989 Mar;9(3):946–958. [PMC free article] [PubMed]
  • Streuli M, Saito H. Regulation of tissue-specific alternative splicing: exon-specific cis-elements govern the splicing of leukocyte common antigen pre-mRNA. EMBO J. 1989 Mar;8(3):787–796. [PMC free article] [PubMed]
  • Reinherz EL, Morimoto C, Fitzgerald KA, Hussey RE, Daley JF, Schlossman SF. Heterogeneity of human T4+ inducer T cells defined by a monoclonal antibody that delineates two functional subpopulations. J Immunol. 1982 Jan;128(1):463–468. [PubMed]
  • Ogata S, Misumi Y, Tsuji E, Takami N, Oda K, Ikehara Y. Identification of the active site residues in dipeptidyl peptidase IV by affinity labeling and site-directed mutagenesis. Biochemistry. 1992 Mar 10;31(9):2582–2587. [PubMed]
  • Kalish RS, Morimoto C. Urushiol (poison ivy)-triggered suppressor T cell clone generated from peripheral blood. J Clin Invest. 1988 Sep;82(3):825–832. [PMC free article] [PubMed]
  • Hong WJ, Doyle D. Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl peptidase IV. J Cell Biol. 1990 Aug;111(2):323–328. [PMC free article] [PubMed]
  • Davis NG, Model P. An artificial anchor domain: hydrophobicity suffices to stop transfer. Cell. 1985 Jun;41(2):607–614. [PubMed]
  • Yaron A, Naider F. Proline-dependent structural and biological properties of peptides and proteins. Crit Rev Biochem Mol Biol. 1993;28(1):31–81. [PubMed]
  • Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C, Nadler LM. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6575–6579. [PMC free article] [PubMed]
  • Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561–569. [PMC free article] [PubMed]
  • Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo VA, Jr, Lombard LA, Gray GS, Nadler LM. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993 Nov 5;262(5135):909–911. [PubMed]
  • Armitage RJ, Fanslow WC, Strockbine L, Sato TA, Clifford KN, Macduff BM, Anderson DM, Gimpel SD, Davis-Smith T, Maliszewski CR, et al. Molecular and biological characterization of a murine ligand for CD40. Nature. 1992 May 7;357(6373):80–82. [PubMed]
  • Fanslow WC, Anderson DM, Grabstein KH, Clark EA, Cosman D, Armitage RJ. Soluble forms of CD40 inhibit biologic responses of human B cells. J Immunol. 1992 Jul 15;149(2):655–660. [PubMed]
  • Rudd C, Helms S, Barber EK, Schlossman SF. The CD4/CD8:p56lck complex in T lymphocytes: a potential mechanism to regulate T-cell growth. Biochem Cell Biol. 1989 Sep;67(9):581–589. [PubMed]
  • Cooke MP, Abraham KM, Forbush KA, Perlmutter RM. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell. 1991 Apr 19;65(2):281–291. [PubMed]
  • Subramanyam M, Gutheil WG, Bachovchin WW, Huber BT. Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. J Immunol. 1993 Mar 15;150(6):2544–2553. [PubMed]
  • Callebaut C, Krust B, Jacotot E, Hovanessian AG. T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science. 1993 Dec 24;262(5142):2045–2050. [PubMed]

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