Abstract
The T-cell activation-Ag CD26 possesses dipeptidyl peptidase IV (DPP IV) enzymatic activity. Costimulatory efficacy and immunocompetence are associated with the enzymatic activity. Goals: In models of experimental cardiac allograft transplantation (HTx), we analyzed the role of CD26/DPP IV during organ rejection. Also, we investigated CD26 enzymatic and cellular expression in human recipients of kidney transplants (Tx). Material and Methods: Heterotopic HTx in rats, models of acute and accelerated rejection. Monitoring of DPP IV serum levels and humoral immunity. Propro-diphenyl phosphonate was employed to inhibit DPP IV activity during rejection. In a prospective study, surface expression of CD26, 3, 4, 8, 45, 122 and ADA on PBL and DPP IV serum activity were measured in kidney recipients for 24 months post-transplantation. Results: Acute rejection was associated with increased serum DPP IV activity (p<0.005). Specific inhibition abrogated acute (p<0.0001) and accelerated (p<0.01) rejection, impairing cytotoxicity and allospecific Ig-synthesis. Kidney recipients displayed a significant drop in CD26 expression on PBL for up to 18 months postoperatively (p<0.001). CD4, 8, 45, 122 and ADA expression kinetics were only briefly affected. DPP IV enzymic activity stayed depressed for at least 12 months (p<0.001). Conclusion: CD26/DPP IV is pivotal in T-cell mediated immune responses toward allo-Ag. In clinical transplantation, engraftment/immunosuppression are reflected by CD26 cellular and enzymatic expression posttransplantation and may serve as an indicator for immunomodulation.
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References
Morimoto, C., and Schlossman, S. F., 1994. CD26 a key costimulatory molecule on CD4 memory cells. The Immunologist 2/1:4–7.
De Meester, I., Korom, S., Van Damme, J., and Scharpsé, S., 1999. CD26, let it cut or cut it down. Immunology Today 20:367–375.
Tanaka, T., Kameoka, J., Yaron, A., Schlossman, S.F., Morimoto, C., 1993. The costimulatory activity of the CD26 antigen requires dipeptidyl peptidase IV enzymatic activity. Proc Natl Acad Sci USA 90:4586–4590.
Tanaka, T., Duke-Cohan, J. S., Kameoka, J., et al. 1994. Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV. Proc Natl Acad Sci USA 91:3082–3086.
Scharpé, S., De Meester, I., Vanhoof, G., et al. 1990. Serum dipeptidyl peptidase IV activity in transplant recipients. Clin Chem 36:984.
Sanda, M.G., Pierson, R., Smith, C., and Rose, E., 1989. Serum dipeptidyl peptidase IV in cardiac transplant recipients. Transplant Proc 21:2525–2526.
Belyaev, A., Borloo, M., Augustyns, K., et al. 1995. A new synthetic method for proline diphenyl phosphonates. Tetrahedron Letters 36:3755–3758.
Lambeir, A.M., Borloo, M., De Meester, I., et. al. 1996. Dipeptidyl-derived diphenyl phosphonate esters: mechanism-based inhibitors of dipeptidyl-peptidase IV. Biochimica Biophys Acta 1290:76–82.
Korom, S., De Meester, I., Stadlbauer, T.H.W., et al. 1997. Inhibition of CD26/dipeptidyl peptidase IV activity in vivo prolongs cardiac allograft survival in rat recipients. Transplantation 63:1495–1500.
Scharpé, S., De Meester, I., Vanhoof, G., Hendriks, D., van Sande, M., Van Camp, K., and Yaron, A., 1988. Assay of dipeptidyl peptidase IV in serum by fluorometry of 4-methoxy-2-naphtylamine. Clinical Chemistry 34:2299–2301.
Binder, J., Lehmann, M., Graser, E., Hancock, W.W., et al., 1996. The effects of nondepleting CD4 targeted therapy in presensitized rat recipients of cardiac allografts. Transplantation 61:804–811.
Fleischer, B., 1987. A novel pathway of human T cell activation via a 103 kD T cell activationmolecule. J Immunol 138:1346–1350.
Dang, N.H., Hafler, D., Schlossman, S.F., and Breitmeyer, J., 1990. FcR-mediated cross-linking of Tal (CDw26) induces human T lymphocyte activation. CellImmunol 125:42–57.
Dang, N.H., Torimoto, Y., Sugita, K., Daley, J.F., Schow, P., Prado, C., Schlossman, S.F., and Morimoro, C., 1990. Cell surface modulation of CD26 by anti-1F7 monoclonal antibody. Analysis of surface expression and human T cell activation. J Immunol 145:3963–3971.
Schön, E., Jahn, S., Kiessig, S.T., et al. 1987. The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur J Immunol 17:1821–1826.
Flentke, G.R., Muñoz, E., Huber, B.T., Plaut, A.G., Kettner, C.A., and Bachovchin, W., 1991. Inhibition of dipeptidyl peptidase 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 USA 88:1556–1559.
Kubota, T., Iizuka, H., Bachovchin, W.W., and Stollar, B.D., 1994. Dipeptidyl peptidase IV (DP IV) activity in serum and on lymphocytes of MRL/Mp-lpr/lpr mice correlates with disease onset. Clin Exp Immunol 96:292–296.
Bednarczyk, J., Caroll, S.M., Marin, C., and McIntyre, B., 1991. Triggering of the proteinase dipeptidyl peptidase IV (CD26) amplifies human T lymphocyte proliferation. J Cell Biochem 46:206–218.
Korom, S., De Meester, I., Schmidbauer, G., et al. 1999. Specific inhibition of CD26/DPP IV enzymatic activity in allograft recipients: effects on humoral immunity. Transplant Proceedings, 31:873.
Korom, S., De Meester, I., Maas, E., et al., 2002. CD26 expression and enzymatic activity in recipients of kidney allografts. Transplant Proceedings, 34:1753–1754.
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Korom, S., De Meester, I., Belyaev, A., Schmidbauer, G., Schwemmle, K. (2004). CD26/DPP IV in Experimental and Clinical Organ Transplantation. In: Back, N., Cohen, I.R., Kritchevsky, D., Lajtha, A., Paoletti, R. (eds) Dipeptidyl Aminopeptidases in Health and Disease. Advances in Experimental Medicine and Biology, vol 524. Springer, Boston, MA. https://doi.org/10.1007/0-306-47920-6_17
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DOI: https://doi.org/10.1007/0-306-47920-6_17
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