Rejection of adoptively transferred Eµ-TCL1 chronic lymphocytic leukemia cells in C57BL/6 substrains or knockout mouse lines

TBET‐expressing Th1 CD4+T cells accumulate in chronic lymphocytic leukaemia without affecting disease progression in Eµ‐TCL1 mice

“…Of note, cytotoxic CD8 + T cell function was shown not to be altered due to deficiency of Tbx21 , whereas IFNγ‐production by NKT cells was reduced (Szabo et al , ). To avoid rejection of TCL1 leukaemia cells after their transplantation in Tbx21 −/− mice, as previously shown in comparable approaches (Öztürk et al , ), Tbx21 −/− BM chimaeras and the respective WT control animals were generated. In addition to this approach, mixed chimaeras were generated by transplantation of a 1:1 mixture of WT and Tbx21 −/− BM cells to distinguish direct effects of Tbx21 ‐deficiency in CD4 + T cells on IFNγ production from indirect effects that might exist in a Tbx21 ‐deficient haematopoietic microenvironment.…”

“…Bone marrow chimaeras were generated as previously described (Öztürk et al , ). In brief, chimaeras were generated by i.v.…”

Meta-Analysis Reveals Significant Sex Differences in Chronic Lymphocytic Leukemia Progression in the Eµ-TCL1 Transgenic Mouse Model

“…However, the number of male and female mice was only specified in a very limited number of papers involving the Eµ-TCL1 transgenic mice, most likely due to unawareness of the significant sex difference in this model. Based on the results of this study, together with the report on the importance of the genetic background of Eµ-TCL1 transgenic mice in the adoptive transplantation setting [41], we urge for more transparent, accurate descriptions of animal models in future publications, including specification of the male-to-female ratio in each study cohort and the accurate genetic substrains of the mice.…”

Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia

“…At the study endpoint 10 weeks after transplantation, leukemic cell load in blood, spleen, and peritoneal cavity (Supplementary Figure S2b), as well as the spleen weight (Supplementary Figure S2c), were significantly higher in the heterozygous control mice compared to the Grn −/− mice. However, in follow-up studies on this experiment and Eμ- TCL1 transplantations to other knockout mouse lines, we could recently provide evidence arguing that the observation of non-engraftment in Grn −/− mice was most likely caused by a CD8 + T cell-mediated immune response of Grn −/− mice against Grn expressing Eμ- TCL1 leukemia cells [89]. The experimental setup was thus not suitable to draw reliable conclusions on the functional relevance of GRN in CLL.…”

“…In addition, in vivo experiments utilizing the Eµ- TCL1 adoptive transfer CLL mouse model reinforced that GRN deficiency in the hematopoietic compartment does not significantly impact on CLL development. A systemic GRN knockout in recipient mice most likely caused a rejection of Eµ- TCL1 cells due to their GRN expression as we have recently discussed [89], and was thus not suitable to draw reliable conclusions on the function of GRN. It has to be considered, that in a knockout model restricted to specific cell-types, GRN-proficient cells might be able to compensate for the loss, as for example seen in a microglia-specific GRN knockout model that did not recapitulate the neurodegenerative phenotype of systemic GRN knockout mice, likely due to neuronal GRN expression [98].…”