Constitutive expression of the pre-TCR enables development of mature T cells

Expression and signalling through the pre-TCR and the TCRαβ resemble two critical checkpoints during T cell development. We investigated to which extent a pre-TCR can functionally replace mature TCRα chains during T cell development. For this purpose, transgenic mice were generated expressing the pre-TCRα (pTα) under the transcriptional control of TCRβ regulatory elements. We report here on the interesting finding that constitutive pTα expression allows complete T cell maturation. The pre-TCR complex permits a subset of β-selected thymocytes to mature in the absence of TCRα into peripheral T cells (βT cells) comprising up to 10% of all lymphocytes. Lymphopenia-driven proliferation of these βT cells is similar to that of conventional αβT cells. Furthermore, βT cells proliferated and acquired effector function upon stimulation with allogeneic MH

Concepts in mature T-cell lymphomas - highlights from an international joint symposium on T-cell immunology and oncology

Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology. We report here meeting highlights on the covered topics of diagnostic pitfalls, implications by the new WHO classification, insights from discovered genomic lesions as well as TCR-centric concepts of cellular dynamics in host defense, auto-immunity and tumorigenic clonal escape, including predictions to be derived from in vivo imaging and mathematical modeling. Presentations on novel treatment approaches were supplemented by strategies of optimizing T-cell immunotherapies. Work packages, that in joint efforts would advance the field of MTCL more efficiently, are identified