Department of Pediatrics II, Pediatric Nephrology, Gastroenterology, Endocrinology and Transplant Medicine, Children's Hospital Essen, Essen, Germany.
Clin Exp Immunol. 2012 May;168(2):251-9. doi: 10.1111/j.1365-2249.2012.04571.x.
The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) have been reported to be associated with allograft rejection. The impact of the expression of immunosuppressive drugs on peripherally circulating CD4(+) T cell subsets after renal transplantation is unknown. Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal allograft recipients participating in a prospective, randomized trial (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids (n = 6), CsA and everolimus plus corticosteroids (n =8) or CsA-free (CsA(free)) receiving everolimus, MPA and corticosteroids (n = 6). After initial reduction of CD4(+) forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(hi) FoxP3(+) regulatory T cells (T(regs)) (P < 0.05; P < 0.01), 3-month post-transplant percentages of T(regs) were reconstituted in CsA(free) and CsA(lo) arms compared to CsA(reg) 12 months post transplant. Expression of CCR5 and CXCR3 on CD4(+) FoxP3(+) and CD4(+) FoxP3(-) T cells 12 months post transplant was increased in CsA(free) versus CsA(reg). Increase in CCR5(+) CXCR3(+) co-expressing CD4(+) FoxP3(-) cells between 3 and 12 months correlated negatively with the glomerular filtration rate (GFR) slope/year [modification of diet in renal disease (MDRD); r = -0.59, P < 0.01]. CsA, but not everolimus, inhibits both T(reg) development and expression of CXCR3 and CCR5 on CD4(+) T cell subsets. Increase in CCR5(+) CXCR3(+) co-expressing CD4(+) FoxP3(-) T cells is associated with early loss in allograft function.
外周趋化因子受体趋化因子受体 3（CXCR3）和 C 型趋化因子受体 5（CCR5）已被报道与同种异体移植物排斥反应有关。免疫抑制药物对肾移植后外周循环 CD4(+)T 细胞亚群的表达的影响尚不清楚。在 20 例参与前瞻性、随机试验（NCT00514514）的肾移植受者中，通过流式细胞术检测 CXCR3 和 CCR5 的表达。初始免疫抑制方案包括巴利昔单抗、环孢素 A（CsA）、吗替麦考酚酯钠和皮质类固醇。3 个月后，患者分别接受 CsA、吗替麦考酚酯钠（MPA）加皮质类固醇（n = 6）、CsA 和依维莫司加皮质类固醇（n = 8）或无 CsA（CsA(free)) 治疗，接受依维莫司、MPA 和皮质类固醇（n = 6）。初始 CD4(+)叉头框蛋白 3（FoxP3)(+)和 CD4(+)CD25(hi)FoxP3(+)调节性 T 细胞（T(regs))（P < 0.05；P < 0.01）减少后，CsA(free)和 CsA(lo)组在移植后 3 个月时 T(regs)的百分比得到重建，而在移植后 12 个月时 CsA(reg)组则减少。与 CsA(reg)相比，CsA(free)组在移植后 12 个月时 CD4(+)FoxP3(+)和 CD4(+)FoxP3(-)T 细胞上 CCR5 和 CXCR3 的表达增加。3 至 12 个月期间，CCR5(+)CXCR3(+)共表达 CD4(+)FoxP3(-)细胞的增加与肾小球滤过率（GFR）斜率/年呈负相关[肾脏病膳食改良（MDRD）；r = -0.59，P < 0.01]。CsA 而不是依维莫司抑制 T(regs)的发育和 CD4(+)T 细胞亚群上 CXCR3 和 CCR5 的表达。CCR5(+)CXCR3(+)共表达 CD4(+)FoxP3(-)T 细胞的增加与同种异体移植物功能的早期丧失有关。
