CHU Sainte-Justine Research Center, Center de Cancérologie Charles-Bruneau, 3175 chemin de la Côte-Ste-Catherine, Montréal, Québec, Canada.
Bone Marrow Transplant. 2012 Mar;47(3):439-50. doi: 10.1038/bmt.2011.93. Epub 2011 May 16.
The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/γc- (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-γ and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34(+) stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.
静脉注射免疫球蛋白（IVIG）预防移植物抗宿主病（GVHD）的疗效尚未得到临床证实。我们利用 NOD/SCID/γc-（NSG）小鼠的异种移植物抗宿主病模型表明，每周给予 IVIG 可显著降低 GVHD 的发生率和相关死亡率，其程度与环孢菌素 A（CsA）相似。与 CsA 和 OKT3 不同，IVIG 不会抑制小鼠体内人 T 细胞的增殖。相反，IVIG 可显著抑制人 IL-17、IL-2、IFN-γ 和 IL-15 的分泌，提示 IVIG 通过免疫调节预防 GVHD。此外，人细胞因子风暴的修饰模式与 CsA 和 OKT3 观察到的不同。最后，在人类重建免疫的小鼠模型中，将 NSG 小鼠植入人 CD34+干细胞，IVIG 可短暂抑制 B 细胞重建，而外周 T 细胞重建和胸腺生成不受影响。这些体内数据引发了关于 IVIG 在 GVHD 预防中的适用性的争论。此外，该模型提供了一个机会，可以进一步阐明 IVIG 抑制 GVHD 的精确机制。
