title: Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL.
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.
authors: Laboratory for Immunological and Molecular Cancer Research, 3rd Medical Department for Hematology, Federal Hospital of Salzburg and Paracelsus Medical Private University, Salzburg, Austria.
authors: J Piñón
authors: JP
authors: Hofbauer
authors: C
authors: C
authors: Heyder
authors: U
authors: U
authors: Denk
authors: T
authors: T
authors: Kocher
authors: C
authors: C
authors: Holler
authors: D
authors: D
authors: Trapin
authors: D
authors: D
authors: Asslaber
authors: I
authors: I
authors: Tinhofer
authors: R
authors: R
authors: Greil
authors: A
authors: A
authors: Egle