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- Title
Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL.
- Authors
Hofbauer, J. Piñón; Heyder, C.; Denk, U.; Kocher, T.; Holler, C.; Trapin, D.; Asslaber, D.; Tinhofer, I.; Greil, R.; Egle, A.
- Abstract
Chronic lymphocytic leukemia (CLL) cells require complex microenvironmental and immunologic interactions to survive and proliferate. Such interactions might be best recreated in animal models; however, this needs extensive verification. We therefore investigated the composition of the T-cell compartment in the Eμ-TCL1 transgenic mouse, currently the most widely used murine model for CLL. Immunophenotyping and transplant approaches were used to define T-cell subsets at various stages of CLL. Analogous to human CLL, we observed a skewing of T-cell subsets from naive to antigen-experienced memory T cells that was more pronounced in lymph nodes than in blood. Transplantation of CLL into non-transgenic recipients was feasible without immunosuppression in a pure C57BL/6 background and resulted in the prominent skewing of the T cells of the recipient mice. Both in spontaneously developed CLL and in the transplantation setting, a loss in T-cell receptor diversity was observed, with a relevant number of clonal T-cell populations arising. This suggests that antigen-dependent differentiation toward the T memory pool is initiated by murine CLL cells. In summary, we validate the TCL1 transgenic mouse model for analysis of T-cell phenotypes and suggest a CLL-dependent antigen-driven skewing of T cells in these mice.
- Subjects
CHRONIC lymphocytic leukemia; T-cell receptor genes; IMMUNOPHENOTYPING; CELL death; CELL proliferation; CD4 antigen; IMMUNOSUPPRESSION; LABORATORY mice
- Publication
Leukemia (08876924), 2011, Vol 25, Issue 9, p1452
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2011.111