Deficient TNF-alpha and IFN-gamma production correlates with nondetectable donor-specific cytotoxicity after clinical kidney transplantation.

Abstract:

BACKGROUND:We previously reported that no cytotoxic T-lymphocyte precursor frequencies (CTLpf) were found in 60% of patients on azathioprine or mycophenolate mofetil+Pred long after kidney transplantation. We questioned whether the absence of donor-specific CTLpf was associated with low levels of stimulatory Th1 (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma) or high levels of regulatory Th2 (interleukin [IL]-4, IL-6, IL-10) cytokines. METHODS:In this study, peripheral blood monocyte cells (PBMC) were stimulated with irradiated donor cells. After 7 days, cytokine production was determined by cytokine bead array, and CTLpf by limiting dilution assay. RESULTS:Patients with detectable CTLpf (> or =10/10(6) PBMC) had significantly higher levels of TNF-alpha (P=0.04) and IFN-gamma (P=0.02) than patients with nondetectable CTLpf (<10/10(6) PBMC). Donor-reactive IL-4, IL-6, and IL-10 production was comparable in both patient groups. Additionally, CTLpf was positively correlated with TNF-alpha (rs=0.54, P=0.0003) and IFN-gamma (rs=0.64, P<0.0001) production. CONCLUSION:The absence of donor-specific CTLp after transplantation correlates with low levels of stimulatory cytokines, not with elevated levels of regulatory cytokines.

journal_name

Transplantation

journal_title

Transplantation

authors

van Besouw NM,de Kuiper R,van der Mast BJ,van de Wetering J,Baan CC,Weimar W

doi

10.1097/TP.0b013e3181a36c85

subject

Has Abstract

pub_date

2009-05-27 00:00:00

pages

1451-4

issue

10

eissn

0041-1337

issn

1534-6080

pii

00007890-200905270-00005

journal_volume

87

pub_type

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