Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1207853 on May 15, 2008

Published online before print May 15, 2008
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(Journal of Leukocyte Biology. 2008;84:380-388.)
© 2008 by Society for Leukocyte Biology

APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis

Gijs Hardenberg*,1, Leticia Fernandez{dagger},1, Jenny Hendriks*, Karim Chebli{dagger}, Chantal Jacquet{dagger}, Marc Sitbon{dagger}, Michel Hahne{dagger},2 and Jan Paul Medema*,2,3

* Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands; and
{dagger} Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier Cedex, France

3 Correspondence: Academic Medical Center, Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Room G2-131, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail j.p.medema{at}amc.nl

ABSTRACT

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.

Key Words: T lymphocyte • TACI • Moloney-murine leukemia virus • Friend-murine leukemia virus






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