Direct activation of antigen-presenting cells is required for CD8+ T-cell priming and tumor vaccination.

Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that APCs could be activated indirectly by proinflammatory mediators synthesized by PAMP-exposed cells. However, data obtained with CD4(+) T cells suggest that inflammatory signals often cannot substitute for direct pattern recognition in APC activation for the priming of T helper responses. To test whether the same is true for CD8(+) T cells, we studied cytotoxic T lymphocyte development in vitro and in mixed chimeric mice in which coexisting APCs can either present a preprocessed model antigen or directly recognize a given PAMP, but not both. We show that indirectly activated APCs promote antigen-specific proliferation of naïve CD8(+) T cells but fail to support their survival and cytotoxic T lymphocyte differentiation. Furthermore, CD8(+) T cells primed by indirectly activated APCs are unable to reject tumors. Thus, inflammation cannot substitute for direct recognition of single PAMPs in CD8(+) T-cell priming. These findings have important practical implications for vaccine design, indicating that adjuvants must be judiciously chosen to trigger the relevant pattern recognition receptors in APCs.

Type I IFN substitutes for T cell help during viral infections.

Certain virus infections depend on the presence of T cell help for the generation of primary CD8(+) T cell responses. However, the mechanisms that render these particular viral infections T cell help dependent is largely unknown. In this study, we compared CD8(+) T cell responses elicited by lymphocytic choriomeningitis virus infection, as prototype of a T cell help independent infection, with T cell help dependent CD8(+) T cell responses induced by vaccinia virus infection. In this paper, we show that a key parameter decisive for T cell help independence is the ability of an infectious agent to stimulate early and robust production of type I IFN. Experimental provision of type I IFN during VV infection rendered the ensuing CD8(+) T cell response completely T cell help independent. Our results support a model in which type I IFN has to be present during the first 3 d of Ag encounter and has to act directly on the responding CD8(+) T cells to promote their survival and effector differentiation. We show that type I IFN signaling on responding CD8(+) T cells induces profound upregulation of CD25 and increased IL-2 expression; however, neither this nor IL-15 accounts for the type I IFN effects on responding CD8(+) T cells. Thus, type I IFN can effectively replace the requirement of T cell help by directly promoting CD8(+) T cell survival and differentiation independent of the type I IFN-induced cytokines IL-2 and IL-15.

Digitale Pflegeanwendungen im Pflegealltag: Zwischen Lösung und neuer Herausforderung.

Digital care applications are digital solutions that should improve or stabilise the health of people in need of care and thus maintain their independence. In the future, they are supposed to be increasingly used to cope with the major challenges in geriatric care, especially the shortage of caregivers. Germany has already created the legal framework for embedding digital care applications in standard care. With the help of DiPA, impairments of independence or abilities of the person in need of care are to be reduced and an aggrevation of the need for care is to be counteracted. In order to successfully adopt these applications, health professionals need to be educated about digital solutions in order to reduce their skepticism and promote trust in these solutions.

Dendritic cells require STAT-1 phosphorylated at its transactivating domain for the induction of peptide-specific CTL.

Phosphorylation of transcription factor STAT-1 on Y701 regulates subcellular localization whereas phosphorylation of the transactivating domain at S727 enhances transcriptional activity. In this study, we investigate the impact of STAT-1 and the importance of transactivating domain phosphorylation on the induction of peptide-specific CTL in presence of the TLR9-dependent immune adjuvant IC31. STAT-1 deficiency completely abolished CTL induction upon immunization, which was strongly reduced in animals carrying the mutation of the S727 phospho-acceptor site. A comparable reduction of CTL was found in mice lacking the type I IFN (IFN-I) receptor, whereas IFN-gamma-deficient mice behaved like wild-type controls. This finding suggests that S727-phosphorylated STAT-1 supports IFN-I-dependent induction of CTL. In adoptive transfer experiments, IFN-I- and S727-phosphorylated STAT-1 were critical for the activation and function of dendritic cells. Mice with a T cell-specific IFN-I receptor ablation did not show impaired CTL responses. Unlike the situation observed for CTL development S727-phosphorylated STAT-1 restrained proliferation of naive CD8(+) T cells both in vitro and following transfer into Rag-deficient mice. In summary, our data reveal a dual role of S727-phosphorylated STAT-1 for dendritic cell maturation as a prerequisite for the induction of CTL activity and for T cell autonomous control of activation-induced or homeostatic proliferation.

Teletherapie ­ eine innovative Therapiemöglichkeit (auch) für ältere Menschen.

Teletherapy enables the provision of therapy services at a distance, supported by the use of information and communication technologies (ICT), for example by means of videoconferencing. This sub-discipline of telemedicine allows, to respond and adapt to global challenges and changing health needs of the population. The Albert Schweitzer Clinic of the Geriatric Health Centers has been using teletherapeutic after-care since the outbreak of the COVID-19 pandemic. The goal is to support patients (Ø 80 years) in carrying out their therapy plan at home after their stay in a geriatric day clinic by using digital media and mobile devices. In this article, we report on their impressions and, together with an expert, explore the question of how teletherapy is being used in Austria.