Levitsky Josh, Miller Joshua, Wang Edward, Rosen Anne, Flaa Cathy, Abecassis Michael, Mathew James, Tambur Anat
Division of Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Hum Immunol. 2009 Mar;70(3):146-50. doi: 10.1016/j.humimm.2008.12.008. Epub 2009 Jan 12.
We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative "regulatory" T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25(high+)Foxp3+ T cells (1.3 +/- 1.0) compared with the non-SRL group (0.7 +/- 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 +/- 0.2) compared with all other subgroups (0.7 +/- 0.6) (p = 0.02). TAC patients showed significantly higher "regulatory" DC2:DC1 ratios (10 +/- 7.6) compared with non-TAC patients (4.1 +/- 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.
我们比较了31例接受不同长期免疫抑制（IS）单一疗法的成年肝移植受者的外周血免疫表型，这些受者接受或未接受移植前阿仑单抗（AL）诱导治疗。所有患者接受西罗莫司（SRL）（n = 10）单一疗法或不接受SRL（他克莫司（TAC）（n = 10）、霉酚酸酯（MMF）（n = 11））单一疗法稳定超过6个月。对假定的“调节性”T细胞和树突状细胞进行了五色流式细胞术检测，并对可溶性HLA-G（sHLA-G）进行了血清检测。与非SRL组（0.7±0.6）相比，SRL单一疗法组的CD4 + CD25（高 +）Foxp3 + T细胞百分比显著更高（1.3±1.0）（p = 0.04）。与所有其他亚组（0.7±0.6）相比，在先前接受AL诱导且无丙型肝炎或排斥反应史的亚组中，SRL的作用甚至更高（1.7±0.2）（p = 0.02）。与非TAC患者（4.1±2.3）相比，TAC患者的“调节性”DC2:DC1比率显著更高（10±7.6）（p = 0.04）。尽管TAC患者的sHLA-G水平似乎更高，但差异无统计学意义。总之，IS单一疗法为研究个体药物的调节作用提供了机会。在部分患者中，SRL维持治疗和先前的AL诱导似乎显示出调节性T细胞免疫表型。然而，TAC患者可能具有其他调节特征，这支持需要进行更大规模的前瞻性研究以阐明差异。
