Tatem L D, Hirpara S, Dalsey R M, Iannacone W M, DeLong W G, Hewitt C W
Department of Surgery, Robert Wood Johnson Medical School, Cooper Health System, USA.
Transplant Proc. 1997 Jun;29(4):2194-5. doi: 10.1016/s0041-1345(97)00292-3.
We hypothesized that an increase in IL-2 activated T cells in situ within the marrow component of a transplanted limb may adversely affect development of tolerance, while increased TGF-beta expression locally would facilitate tolerance induction and/or maintenance. Digital image analysis of cellular expression of IL-2r in the bone marrow was significantly increased in the CON and TXP limbs for both GVHD and tolerant recipients as compared to normal limb marrow (P < .02). The amount of cellular expression of TGF-beta was significantly increased in the GVHD animals, both CON and TXP, as compared to the tolerant animals (43.2 +/- 3.1 vs 10.6 +/- 2.6; P < .000001). Our results show that increased IL-2r and TGF-beta expression in situ within the bone marrow is an important effect common to both alloimmune tolerance and GVHD induction with VBMT chimeras. The dramatic increase in the expression of TGF-beta in the GVHD transplanted limbs may explain the profound immunosuppression that results. Additionally, moderate expression of TGF-beta in situ in tolerant chimeras may represent a mechanism for the induction and maintenance of tolerance.
我们推测，移植肢体骨髓成分中白细胞介素-2激活的T细胞原位增加可能会对耐受性的发展产生不利影响，而局部转化生长因子-β表达增加则会促进耐受性的诱导和/或维持。与正常肢体骨髓相比，移植物抗宿主病（GVHD）和耐受受体的对照（CON）和移植（TXP）肢体骨髓中白细胞介素-2受体（IL-2r）的细胞表达的数字图像分析均显著增加（P < 0.02）。与耐受动物相比，GVHD动物（包括CON和TXP）中转化生长因子-β的细胞表达量显著增加（43.2 ± 3.1对10.6 ± 2.6；P < 0.000001）。我们的结果表明，骨髓中IL-2r和转化生长因子-β原位表达增加是同种异体免疫耐受和VBMT嵌合体诱导GVHD的共同重要效应。GVHD移植肢体中转化生长因子-β表达的显著增加可能解释了由此导致的深度免疫抑制。此外，耐受嵌合体中转化生长因子-β的适度原位表达可能代表了诱导和维持耐受性的一种机制。
