Association of peripheral NK cell counts with Helios(+)IFN-gamma(-) T-regs in patients with good long-term renal allograft function

作者：Trojan, K.; Zhu, L.; Aly, M.; Weimer, R.; Bulut, N.; Morath, C.; Opelz, G.; Daniel, V.^*

来源：Clinical and Experimental Immunology, 2017, 188(3): 467-479.

DOI：10.1111/cei.12945

• CD8(+) lymphocytes
• CTLA-4
• good long-term renal allograft function
• glomerular filtration rate
• Helios(+)IFN-gamma(-) T-reg
• peripheral NK cells
• serum creatinine
• TGF-beta
• T-reg subsets

Little is known about a possible interaction of natural killer (NK) cells with regulatory T cells (T-reg) in long-term stable kidney transplant recipients. Absolute counts of lymphocyte and Treg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-colour fluorescence flow cytometry. Patients were 1946 +/- 2201 days (153-10 268 days) post-transplant and showed a serum creatinine of 1.7 +/- 0.7 mg/dl. Renal transplant recipients investigated > 1.5 years post-transplant showed higher total NK cell counts than recipients studied < 1.5 years after transplantation (P = 0.006). High NK cells were associated with high glomerular filtration rate (P = 0.002) and low serum creatinine (P = 0.005). Interestingly, high NK cells were associated with high CD4(+) CD25(+) CD127(-) forkhead box protein 3 (FoxP3 (+)) T-reg that co-express the phenotype Helios(+)interferon (IFN)-gamma(-) and appear to have stable FoxP3 expression and originate from the thymus. Furthermore, high total NK cells were associated with T-reg that co-express the phenotypes interleukin (IL)-10(-) transforming growth factor (TGF)-beta(+) (P = 0.013), CD183(+)CD62L(-) (P = 0.003), CD183(+)CD62(+) (P = 0.001), CD183(-)CD62L(+) (P = 0.002), CD252(-)CD152(+) (P < 0.001), CD28(+) human leucocyte antigen D-related (HLA-DR-) (P = 0.002), CD28(+) HLA-DR+ (P < 0.001), CD95(+)CD178(-) (P < 0.001) and CD279(-)CD152(+) (P < 0.001), suggesting that these activated T-reg home in peripheral tissues and suppress effector cells via TGF-beta and cytotoxic T lymphocyte associated protein 4 (CTLA-4). The higher numbers of NK and T-reg cell counts in patients with long-term good allograft function and the statistical association of these two lymphocyte subsets with each other suggest a direct or indirect (via DC) interaction of these cell subpopulations that contributes to good long-term allograft acceptance. Moreover, we speculate that regulatory NK cells are formed late post- transplant that are able to inhibit graft- reactive effector cells.

• 出版日期2017-6
• 单位华中科技大学