CD26/DPP IV in experimental and clinical organ transplantation.
The T-cell activation-Ag CD26 possesses dipeptidyl peptidase IV (DPP IV) enzymatic activity. Costimulatory efficacy and immunocompetence are associated with the enzymatic activity.


OBJECTIVE
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).


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).


CONCLUSIONS
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.
Korom
Stephan
S
Dept. of General and Thoracic Surgery, Justus Liebig University, Giessen, Germany.
de Meester
Ingrid
I
Belyaev
A
A
Schmidbauer
Georg
G
Schwemmle
Konrad
K
D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000276:immunology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D063065:Organophosphonates / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000276:immunology
D015703:Antigens, CD; D007518:Isoantibodies; D063065:Organophosphonates; D018819:Dipeptidyl Peptidase 4; D008666:Metalloendopeptidases