Baan C C, Knoop C J, van Gelder T, Holweg C T, Niesters H G, Smeets T J, van der Ham F, Zondervan P E, Maat L P, Balk A H, Weimar W
Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Transplantation. 1999 Mar 27;67(6):870-6. doi: 10.1097/00007890-199903270-00014.
Despite blockade of the interleukin-2/interleukin 2 receptor (IL-2/IL-2R) pathway by the murine anti-CD25 (i.e., IL-2R alpha chain) monoclonal antibody BT563, cardiac rejection can still occur. In these cases, growth factors other than IL-2 may contribute to allograft rejection. We studied the expression of IL-15, a macrophage-derived cytokine associated with T-cell activation, which interacts with the beta and gamma chains of the IL-2R during rejection episodes under anti-CD25 therapy.
We measured intragraft IL-15 mRNA expression and the number of IL-15- and CD68-positive cells in posttransplantation endomyocardial biopsies (EMBs; n=45) and in nontransplanted, donor-heart specimens (n=11) by competitive template reverse transcription-polymerase chain reaction and immunohistochemistry, respectively.
IL-15 mRNA expression was present in the majority of posttransplantation EMB specimens (91%, 41/45) and in nontransplanted donor-heart specimens (91%, 10/11). Relative IL-15 mRNA levels were neither associated with transplantation nor with rejection status. After transplantation, the number of IL-15- and CD68-positive cells significantly increased (P<0.001), but IL-15-positive cell counts did not reflect the histological rejection grade. Anti-CD25 treatment, in contrast to its effects on the IL-2/IL-2R complex, had no influence on intragraft IL-15 mRNA and protein production. In rejection EMB specimens, during (n=5) and after (n=8) anti-CD25 therapy, no differences in relative IL-15 mRNA levels, or in IL-15- and CD68-positive cell counts, were measured.
After heart transplantation, high numbers of IL-15- and CD68-positive cells infiltrate the graft. This phenomenon is independent of the rejection status. IL-15 remains present during blockade of the IL-2/IL-2R pathway by anti-CD25 monoclonal antibodies, and it may participate in T cell-dependent donor-directed immune responses, thereby explaining the occurrence of rejection in the absence of IL-2.
尽管鼠源性抗CD25（即白细胞介素-2受体α链）单克隆抗体BT563阻断了白细胞介素-2/白细胞介素2受体（IL-2/IL-2R）通路，但心脏排斥反应仍可能发生。在这些情况下，除IL-2外的生长因子可能促成同种异体移植排斥反应。我们研究了IL-15的表达，IL-15是一种与T细胞活化相关的巨噬细胞衍生细胞因子，在抗CD25治疗的排斥反应发作期间，它与IL-2R的β链和γ链相互作用。
我们分别通过竞争性模板逆转录-聚合酶链反应和免疫组织化学方法，测量了移植后心内膜心肌活检标本（EMB；n = 45）和未移植的供心标本（n = 11）中移植物内IL-15 mRNA表达以及IL-15和CD68阳性细胞的数量。
大多数移植后EMB标本（91%，41/45）和未移植的供心标本（91%，10/11）中均存在IL-15 mRNA表达。相对IL-15 mRNA水平既与移植无关，也与排斥状态无关。移植后，IL-15和CD68阳性细胞数量显著增加（P<0.001），但IL-15阳性细胞计数不能反映组织学排斥分级。与抗CD25对IL-2/IL-2R复合物的作用相反，抗CD25治疗对移植物内IL-15 mRNA和蛋白产生没有影响。在抗CD25治疗期间（n = 5）和治疗后（n = 8）的排斥EMB标本中，未检测到相对IL-15 mRNA水平或IL-15和CD68阳性细胞计数的差异。
心脏移植后，大量IL-15和CD68阳性细胞浸润移植物。这种现象与排斥状态无关。在抗CD25单克隆抗体阻断IL-2/IL-2R通路期间，IL-15仍然存在，它可能参与T细胞依赖性供体定向免疫反应，从而解释了在没有IL-2的情况下排斥反应的发生。
