A novel mouse model for Sézary syndrome using xenotransplantation of Sézary cells into immunodeficient RAG2(-/-) γc(-/-) mice.
Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with CD4+ tumor cells localized in the skin, lymph nodes and peripheral blood. Characteristic molecular aberrancies in SS have been identified; however, paucity of functional models severely hampered the translation of these observations into pathogenic mechanisms, and subsequent validation of novel therapeutic targets. We therefore developed a mouse model for SS using intrahepatic injection of SS cells in newborn immunodeficient RAG2(-/-)  γc(-/-)  mice that are completely devoid of T-, B- and NK-cell activity. Injection of the SS cell line SeAx led to long-term and reproducible systemic repopulation of the mice. Injection of mice with the SS cell line HuT-78 led to the death of the mice owing to massive growth of internal tumors. Four weeks after injection of primary SS cells, human CD3+ T cells could be tracked back in the liver, peripheral blood, lymph nodes, spleen and skin of the mice, although the engraftment rate varied when using cells from different patients. In conclusion, we demonstrate that injection of SS cell lines or primary cells in newborn RAG2(-/-)  γc(-/-)  mice results in long-term systemic repopulation of the mice, thereby providing a novel mouse model for Sézary syndrome.
Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands. l.vanderfits@lumc.nl
Leslie
L
van der Fits
Heggert G
HG
Rebel
Jacoba J
JJ
Out-Luiting
Stephan M
SM
Pouw
Fiona
F
Smit
Kim G
KG
Vermeer
Lisanne
L
van Zijl
Cornelis P
CP
Tensen
Kees
K
Weijer
Maarten H
MH
Vermeer
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012751:Sezary Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D004268:DNA-Binding Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D019394:Ki-67 Antigen; C499308:Rag2 protein, mouse