CD26/DPP IV in experimental and clinical organ transplantation

Adv Exp Med Biol. 2003:524:133-43. doi: 10.1007/0-306-47920-6_17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / blood
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl Peptidase 4 / immunology*
  • Dipeptidyl Peptidase 4 / metabolism
  • Graft Rejection / blood
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Heart Transplantation / immunology*
  • Humans
  • Isoantibodies / blood
  • Kidney Transplantation / immunology*
  • Metalloendopeptidases / antagonists & inhibitors*
  • Models, Animal
  • Organophosphonates / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • Transplantation, Homologous / immunology

Substances

  • Antigens, CD
  • Isoantibodies
  • Organophosphonates
  • Dipeptidyl Peptidase 4
  • Metalloendopeptidases