Origin and Transformation of T Cell Progenitors

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• Professor Hans-Reimer Rodewald, German Cancer Research Center, Heidelberg
• Wednesday 30 November 2011, 12:30-13:30
• Lecture Theatre, Department of Pathology, Tennis Court Road.

If you have a question about this talk, please contact Sue Griffin.

Host: Jim Kaufman, jfk31@cam.ac.uk

We mapped the origin of the majority of T cell progenitors in the thymus to an interleukin 7 receptor (Il7r)-expressing progenitor, consistent with a lymphoid-primed route from bone marrow to thymus. Most of these T cell progenitors lacked myeloid potential in vivo, which argues against the recent notion that T cells and myeloid cells in the thymus share a common progenitor.

By contrast, using a T cell-biased Cre-deleter, we found that Notch1-deficient T cell progenitors were blocked in their T cell development, and gave rise to B cells as well as conventional and plasmacytoid dendritic cells in the thymus. A hallmark of T cell progenitors is their lack of self-renewal.

Hence, thymus function is thought to absolutely depend on continuous supply of new progenitors from the bone marrow. We uncovered the ability of the thymus for autonomous, i.e. bone marrow-independent T cell development. Normally, fit progenitors from the bone marrow prevail over exhausted progenitors in the thymus. Progenitor deprivation resulted in persistence of thymocytes, which frequently results in T cell acute lymphoblastic leukemia (T-ALL) arising in the thymus. These T-ALL share cellular and molecular hallmarks of human T-ALL.

These findings suggest that perturbed progenitor turnover can cause genomic instability and cancer.

This talk is part of the Immunology in Pathology series.

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