APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis.
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.
Hardenberg
Gijs
G
Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Fernandez
Leticia
L
Hendriks
Jenny
J
Chebli
Karim
K
Jacquet
Chantal
C
Sitbon
Marc
M
Hahne
Michel
M
Medema
Jan Paul
JP
D000818:Animals; D015551:Autoimmunity; D005434:Flow Cytometry; D006400:Hematocrit; D006579:Heterozygote; D006720:Homozygote; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology* / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000276:immunology / Q000472:pathogenicity; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D010047:Ovalbumin