Cultures of Kidney Transplant Fine-Needle Aspiration Samples from Rejection-Free Patients Produce a Specific Antidonor Response Suppressive Factor

Abstract

Background/Aims: 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-γ, TGF-β1, TGF-β2, GM-CSF, and PGE₂ 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 PGE₂ 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.