Recent Advances In T Cell Biology New Ligands New Functions And New Translational Perspectives

Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional α/β T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and >95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells. Dieter Kabelitz & Julie Déchanet-Merville

This book presents current understanding of the importance of modern immunology in the etiopathogenesis of human diseases and explores how this understanding is impacting on diagnosis, prognosis, treatment, and prophylaxis. As the core of modern immunology, the “danger/injury model” is introduced and addressed throughout the book. Volume I of the book describes the network of damage-associated molecular pattern molecules (DAMPs) and examines the central role of DAMPs in cellular stress responses and associated regulated cell death, the promotion and resolution of inflammation, the activation of innate lymphoid cells and unconventional T cells, the stimulation of adaptive immunity, and tissue repair. The significance of DAMPs in a wide range of human diseases will then be explored in Volume II of the book, with discussion of the implications of injury-induced innate immunity for present and future treatments. This book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from immunity and inflammation research into clinical practice. The readership will include practitioners and clinicians such as hematologists, rheumatologists, traumatologists, oncologists, intensive care anesthetists, endocrinologists such as diabetologists, psychiatrists, neurologists, pharmacists, and transplantologists.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of Springer Nature’s longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the 20th volume of a continuing series.

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation: Models in Discovery and Translation, Second Edition once again provides clinical and scientific researchers with a deep understanding of the current research in this field and the implications for translational practice. By providing an overview of the immune biology of HSCT, an explanation of immune rejection, and detail on antigens and their role in HSCT success, this book embraces biologists and clinicians who need a broad view of the deeply complex processes involved. It then moves on to discuss the immunobiology mechanisms that influence graft-versus-host disease (GVHD), graft-versus-leukemia effect, and transplantation success. Using illustrative figures, highlighting key issues, describing recent successes, and discussing unanswered questions, this book sums up the current state of HSCT to enhance the prospects for the future. The second edition is fully revised and includes new chapters on microbiome, metabolism, kinase targets, micro-RNA and mRNA regulatory mechanisms, signaling pathways in GVHD, innate lymphoid system development, recovery and function in GVHD, genetically engineered T-cell therapies, immune system engagers for GVHD and graft-versus-tumor, and hematopoietic cell transplant for tolerance induction in solid organ grafts. Brings together perspectives from leading laboratories and clinical research groups to highlight advances from bench to the bedside Guides readers through the caveats that must be considered when drawing conclusions from studies with animal models before correlating to clinical allogeneic hematopoietic stem cell transplantation (HSCT) scenarios Categorizes the published advances in various aspects of immune biology of allogeneic HSCT to illustrate opportunities for clinical applications