Deficient TNF-α and IFN-γ production correlates with nondetectable donor-specific cytotoxicity after clinical kidney transplantation
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]-α, interferon [IFN]-α) 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 (ĝ‰¥10/10 PBMC) had significantly higher levels of TNF-α (P=0.04) and IFN-α (P=0.02) than patients with nondetectable CTLpf (<10/10 PBMC). Donor-reactive IL-4, IL-6, and IL-10 production was comparable in both patient groups. Additionally, CTLpf was positively correlated with TNF-α (rs=0.54, P=0.0003) and IFN-α (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.