Cultures of kidney transplant fine-needle aspiration samples from rejection-free patients produce a specific antidonor response suppressive factor.
OBJECTIVE
Growth of T cell lines from kidney graft biopsy specimens that suppress the antidonor response, either directly or through a soluble factor, both specific and nonspecific to donor, has been reported. Fine-needle aspiration biopsy sample cultures synthesize a large array of cytokines/chemokines with significant differences between stable versus acute rejection transplants. We hypothesize that the products of such cultures may be endowed with antidonor response modulation abilities in kidney transplantation.


METHODS
From 46 patients, 21 rejection free (group A) and 25 developing 28 acute rejection crises (group B), samples were obtained on days 7 and 30 after transplantation in group A and on day 7 and on acute rejection day in group B. The supernatants obtained after 48 h of culture were studied for IL-1 receptor antagonist, IL-4, IL-4 soluble receptor alpha, IL-12, IL-13, IFN-gamma, TGF-beta1, TGF-beta2, GM-CSF, and PGE(2) and for their effects on mixed lymphocyte reactions, donor-recipient and recipient-third-party combinations. At the end, analysis by flow cytometry of donor-recipient cultures complemented the analysis done before cultures.


RESULTS
Day 7 supernatants from group A specifically and significantly inhibited the antidonor response; supernatants from group B nonspecifically stimulated the antidonor response. The IL-1 receptor antagonist production was significantly higher by day 7 in group A, and the PGE(2) production was significantly higher in group B. Flow cytometry analysis did not disclose significant differences between inhibited versus stimulated antidonor responses.


CONCLUSIONS
Cultures of aspiration biopsy samples done early after transplantation in rejection-free patients produce soluble suppression-specific antidonor response factor(s), not present in cultures from biopsy specimens taken before and during rejection. This was associated with IL-1 receptor antagonist synthesis.
Department of Nephrology, Hospital S. João, Porto, Portugal. gerardooliveira@mail.telepac.pt
José Gerardo G
JG
de Oliveira
Paula
P
Xavier
João
J
Ramos
Susana
S
Sampaio
Maria
M
Magalhães
Armando
A
Mendes
Manuel
M
Pestana
D000293:Adolescent; D000328:Adult; D001685:Biological Factors / Q000494:pharmacology*; D003470:Culture Media; D046508:Culture Techniques; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged
D001685:Biological Factors; D003470:Culture Media; D007166:Immunosuppressive Agents