TGF-ß signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.

TGF-ß is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-ß receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-ß-driven peripheral tolerance is not regulated by TGF-ß signalling on mature CD4⁺ T cells. Inducible TR2 ablation specifically on CD4⁺ T cells did not result in a lethal autoinflammation. Transfer of these TR2-deficient CD4⁺ T cells to lymphopenic recipients resulted in colitis, but not overt autoimmunity. In contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4⁺ T cells does not result in the collapse of the T(reg) cell population as observed in constitutive models. Instead, a pronounced enlargement of both regulatory and effector memory T cell pools was observed. This expansion is cell-intrinsic and seems to be caused by increased T cell receptor sensitivity independently of common gamma chain-dependent cytokine signals. The expression of Foxp3 and other regulatory T cells markers was not dependent on TGF-ß signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-ß signalling on mature CD4⁺ T cells is not responsible for breakdown of peripheral tolerance, but rather controls homeostasis of mature T cells in adult mice.

Integrating heterogeneous odor response data into a common response model: A DoOR to the complete olfactome.

We have developed a new computational framework for merging odor response data sets from heterogeneous studies, creating a consensus metadatabase, the database of odor responses (DoOR). As a result, we obtained a functional atlas of all available odor responses in Drosophila melanogaster. Both the program and the data set are freely accessible and downloadable on the Internet (http://neuro.uni-konstanz.de/DoOR). The procedure can be adapted to other species, thus creating a family of "olfactomes" in the near future. Drosophila melanogaster was chosen because of all species this one is closest to having the complete olfactome characterized, with the highest number of deorphanized receptors available. The database guarantees long-term stability (by offering time-stamped, downloadable versions), up-to-date accuracy (by including new data sets as soon as they are published), and portability (for other species). We hope that this comprehensive repository of odor response profiles will be useful to the olfactory community and to computational neuroscientists alike.