Immunology

Immune responses are efficient because the rare antigen-specific naïve cells are able to proliferate extensively and accumulate upon antigen stimulation. Moreover, differentiation into memory cells actually increases T cell accumulation, indicating improved productive division in secondary immune responses. These properties raise an important paradox: how T cells may survive the DNA lesions necessarily induced during their extensive division without undergoing transformation. We here present the first data addressing the DNA damage responses (DDRs) of CD8 T cells in vivo during exponential expansion in primary and secondary responses in mice. We show that during exponential division CD8 T cells engage unique DDRs, which are not present in other exponentially dividing cells, in T lymphocytes after UV or X irradiation or in non-metastatic tumor cells. While in other cell types a single DDR pathway is affected, all DDR pathways and cell cycle checkpoints are affected in dividing CD8 T cells. All DDR pathways collapse in secondary responses in the absence of CD4 help. CD8 T cells are driven to compulsive suicidal divisions preventing the propagation of DNA lesions. In contrast, in the presence of CD4 help all the DDR pathways are up regulated, resembling those present in metastatic tumors. However, this up regulation is present only during the expansion phase; i.e., their dependence on antigen stimulation prevents CD8 transformation. These results explain how CD8 T cells maintain genome integrity in spite of their extensive division, and highlight the fundamental role of DDRs in the efficiency of CD8 immune responses.

This study provides a comprehensive analysis of the cytokine patterns of CD4+ T cell responses in 20 humans after TBE vaccination in comparison to those in 18 patients with TBEV infection. Specifically, Th1-specific cytokines (IFN-γ, IL-2, TNF-α), CD40 ligand and the Th1 lineage-specifying transcription factor Tbet were determined upon stimulation with peptides covering the TBEV structural proteins contained in the vaccine (C-capsid, prM/M-membrane and E-envelope). We show that TBEV-specific CD4+ T cell responses are polyfunctional, but the cytokine patterns after vaccination differed from those after infection. TBE vaccine responses were characterized by lower IFN-γ responses and high proportions of TNF-α+IL-2+cells. In vaccine-induced responses—consistent with the reduced IFN-γ expression patterns—less than 50% of TBEV peptides were detected by IFN-γ+ cells as compared to 96% detected by IL-2+ cells, indicating that the single use of IFN-γ as a read-out strongly underestimates the magnitude and breadth of such responses. The results provide important insights into the functionalities of CD4+ T cells that coordinate vaccine responses and have direct implications for future studies that address epitope specificity and breadth of these responses.

"Science Immunology   will feature interdisciplinary research focused on the understanding of problems in cellular and clinical immunology, including links to microbiology."

Both are scheduled to begin publishing papers in mid-2016.

The new journals reflect the association's mission to advance science, engineering, and innovation throughout the world, for the benefit of all people, AAAS CEO Rush Holt said. "Since 1848, the AAAS mission has called on us to foster communication among scientists, engineers, and the public," said Holt, executive publisher of the Science family of journals. "Toward that end, we edit and publish Science, the world's finest weekly for research communication and general science news, and in recent years, we have added other outstanding research journals. Science Robotics and Science Immunology are a further fulfillment of our non-profit mission."

Publisher Kent Anderson described Science Robotics as an interdisciplinary journal spanning the basic sciences, computer science, and engineering. "It will cover new developments in robotics and associated advances in materials research, for example, as well as artificial intelligence, sensors, and human-machine interactions," he added.

Science Immunology will encompass all aspects of immunology, featuring studies of the immune system in all organisms, including human and cancer immunology. "Its focus will be primarily on basic research, through preclinical studies and appropriate Phase I trials," Anderson explained.

Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non-inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation-induced ligand), are essential not only for the long-term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non-inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut – the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class-switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long-term humoral immune protection, as they are crucial for the longevity of antibody-producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis.