Zusammenfassung. Die Berliner Social Support Skalen (BSSS; Schwarzer & Schulz, 2000 ) unterscheiden sich von anderen Fragebogenverfahren zur sozialen Unterstützung durch ihren mehrdimensionalen Ansatz: Sowohl kognitive als auch behaviorale Aspekte sozialer Unterstützung können mit den insgesamt 6 Skalen (Wahrgenommene, Erhaltene und Geleistete Unterstützung, Bedürfnis und Suche nach Unterstützung, Protektives Abfedern) erhoben werden. Die vorliegende Untersuchung beruht auf einer Stichprobe von 457 Krebspatienten, die mehrmals vor und nach einer Operation befragt wurden. In dieser Studie erwiesen sich die Skalen als psychometrisch befriedigend. Zahlreiche Hinweise auf die Validität konnten ermittelt werden. Unter anderem war es möglich, auch die erhaltene Patientenunterstützung durch die Unterstützung seitens des Partners vorherzusagen. Das beschriebene Inventar steht unter http://www.coping.de zur Verfügung.

Suppression by T regulatory (Tr) cells is essential for the induction of peripheral tolerance. Many types of CD4+ Tr cells have been described in a number of systems, and although the precise mechanisms which mediate their effects remain to be defined, it is well established that they can suppress immune responses via cell-cell interactions and/or the production of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). Type 1 T regulatory (Tr1) cells are defined by their ability to produce high levels of IL-10 and TGF-β, and these cytokines mediate their ability to suppress pathological immune responses in the settings of transplantation, allergy and autoimmune disease. Tr1 cell activity is not necessarily beneficial, and they can also suppress immune responses to antigens from tumours and pathogens. In vivo, the differentiation of Tr1 cells is likely controlled by certain dendritic cells which promote IL-10 production and may express tolerogenic costimulatory molecules. Another subset of CD4+ Tr cells is defined by constitutive expression of CD25, and although these CD4+CD25+ Tr cells appear to suppress via mechanisms which are largely independent of cytokines, they may actively promote the differentiation of Tr1 cells. Many questions about the basic biology of Tr1 cells remain to be answered, but the development of therapeutic strategies designed to harness their immunoregulatory effects can already be contemplated.

As part of a systematic screen for novel imprinted genes of human chromosome 7 we have investigated GRB10, which belongs to a small family of adapter proteins, known to interact with a number of receptor tyrosine kinases and signalling molecules. Upon allele-specific transcription analysis involving multiple distinct splice variants in various fetal tissues, we found that human GRB10 is imprinted in a highly isoform- and tissue-specific manner. In fetal brains, most variants are transcribed exclusively from the paternal allele. Imprinted expression in this tissue is not accompanied by allele-specific methylation of the most 5' CpG island. In skeletal muscle, one GRB10 isoform, gamma1, is expressed from the maternal allele alone, whereas in numerous other fetal tissues, all GRB10 splice variants are transcribed from both parental alleles. A remarkable finding is paternal-specific expression of GRB10 in the human fetal brain, since, in the mouse, this gene is transcribed exclusively from the maternal allele. To our knowledge, this is the first example of a gene that is oppositely imprinted in mouse and human.

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Background CD4+ regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies. Design and MethodsThe ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported. ResultsInterleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-β independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors. ConclusionsBased on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies. therapy. Haematologica 2010;95(12): 2134-2143. doi:10.3324/haematol.2010 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Key words: regulatory T cells, immune responses, exogenous recombinant human IL-10. Citation: Bacchetta R, Gregori S, Serafini G, Sartirana C, Schulz U, Zino E, Tomiuk S, Jansen U, Ponzoni M, Paties CT, Fleischhauer K, and Roncarolo MG. Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy