Hardenberg Gijs, Fernandez Leticia, Hendriks Jenny, Chebli Karim, Jacquet Chantal, Sitbon Marc, Hahne Michel, Medema Jan Paul
Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
J Leukoc Biol. 2008 Aug;84(2):380-8. doi: 10.1189/jlb.1207853. Epub 2008 May 15.
The TNF family member, a proliferation-inducing ligand (APRIL), has been suggested to act as a costimulatory molecule in T cell responses. However, studies addressing this role in vivo are largely lacking. Here, we evaluated the effects of APRIL on physiological T cell responses in vivo. Although receptors for APRIL are expressed on a subset of T cells, neither TCR transgenic (Tg) T cell responses nor endogenous TCR responses were affected by Tg APRIL expression in vivo. Moreover, APRIL did not significantly enhance the induction of T cell lymphomas upon Moloney murine leukemia virus (MLV) infection. This clearly contrasts current belief and indicates that APRIL does not serve a major role in T cell immunity or lymphomagenesis. However, we did observe a strong increase in erythroleukemia formation after MLV inoculation of APRIL Tg mice. Strikingly, this erythroleukemia-facilitating property of APRIL was confirmed using the erythroleukemogenic Friend-MLV. Erythroleukemia in APRIL Tg mice was characterized by low hematocrits and grossly enlarged spleens with an increased percentage of erythroid precursors. Altogether, these results unveil new proerythroleukemogenic properties of APRIL.
肿瘤坏死因子（TNF）家族成员增殖诱导配体（APRIL）被认为在T细胞应答中作为共刺激分子发挥作用。然而，目前在很大程度上缺乏针对其在体内这一作用的研究。在此，我们评估了APRIL对体内生理性T细胞应答的影响。尽管APRIL的受体在一部分T细胞上表达，但在体内，TCR转基因（Tg）T细胞应答和内源性TCR应答均未受Tg APRIL表达的影响。此外，在莫洛尼鼠白血病病毒（MLV）感染后，APRIL并未显著增强T细胞淋巴瘤的诱导。这明显与当前的认知相悖，表明APRIL在T细胞免疫或淋巴瘤发生过程中并不起主要作用。然而，我们确实观察到，在给APRIL Tg小鼠接种MLV后，红白血病的形成显著增加。引人注目的是，使用致红白血病的弗氏MLV证实了APRIL的这种促进红白血病发生的特性。APRIL Tg小鼠的红白血病特征为血细胞比容降低、脾脏明显肿大以及红系前体细胞百分比增加。总之，这些结果揭示了APRIL新的促红白血病发生特性。
