ResearchPad - opinions-and-reviews https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Insights into CD8 T Cell Activation and Exhaustion from a Mouse Gammaherpesvirus Model]]> https://www.researchpad.co/article/Na501c9d8-fc34-42e5-a600-2e37987884b1 (S.R.S.) I was introduced to viral immunology while working in Peter Doherty's laboratory in the early stages of my research career, inspiring a lifelong interest in this area. During those early years under Peter's mentorship, we studied a mouse gammaherpesvirus model (murine gammaherpesvirus-68 [MHV-68]) that provided a useful small animal model for investigating the immunological control of gammaherpesvirus infection. Interestingly, while CD4 T cells were not required for acute control of MHV-68 in the lung, CD8 T cell-mediated control was progressively lost in the absence of CD4 T cell help, leading to viral recrudescence. This was one of several early studies showing that CD8 T cell control of persistent viral infections was lost in the absence of CD4 T cell help, preceding the concept of CD8 T cell exhaustion. Further studies showed that MHV-68 infection of mice offered a unique model for comparing the mechanisms of acute and long-term control of a persistent viral infection and developing strategies for reversing T cell exhaustion. Here, we provide a brief review of the literature on CD8 T cell activation and exhaustion in this model, focusing on the role of CD40 and B7 family members and including some previously unpublished data.

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<![CDATA[Harnessing Cross-Reactive CD8<sup>+</sup> T<sub>RM</sub> Cells for Long-Standing Protection Against Influenza A Virus]]> https://www.researchpad.co/article/N78e0dd96-2a85-494c-8baf-08c58a02365c <![CDATA[From Superantigens to “Real” Viral Antigens]]> https://www.researchpad.co/article/N18bb9dcf-b77a-445f-8915-4965431dc048 Studies inspired by Dr. Peter Doherty led to over 16 years of research into the mouse gamma-herpesvirus, γHV68, in the Blackman laboratory. Progress on our understanding of γHV68 biology include insight into the establishment of latency, immune control of the acute and latent stages of infection and experimental vaccines, is described here.

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<![CDATA[Recognition of Apoptotic Cells by Viruses and Cytolytic Lymphocytes: Target Selection in the Fog of War]]> https://www.researchpad.co/article/Ne2b6a2ff-e011-4649-9fd9-ca334a576a48 Viruses and cytolytic lymphocytes operate in an environment filled with dying and dead cells, and cell fragments. For viruses, irreversible fusion with doomed cells is suicide. For cytotoxic T lymphocyte and natural killer cells, time and limited lytic resources spent on apoptotic targets is wasteful and may result in death of the host. We make the case that the target membrane cytoskeleton is the best source of information regarding the suitability of potential targets for engagement for both viruses and lytic effector cells, and we present experimental evidence for detection of apoptotic cells by HIV, without loss of infectivity.

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<![CDATA[Immune Control of <i>γ</i>-Herpesviruses]]> https://www.researchpad.co/article/Nac5025be-af6f-48ce-b3bb-d64b44a73bf4 Vaccination against γ-herpesviruses has been hampered by our limited understanding of their normal control. Epstein–Barr virus (EBV)-transformed B cells are killed by viral latency antigen-specific CD8+ T cells in vitro, but attempts to block B cell infection with antibody or to prime anti-viral CD8+ T cells have protected poorly in vivo. The Doherty laboratory used Murid Herpesvirus-4 (MuHV-4) to analyze γ-herpesvirus control in mice and found CD4+ T cell dependence, with viral evasion limiting CD8+ T cell function. MuHV-4 colonizes germinal center (GC) B cells via lytic transfer from myeloid cells, and CD4+ T cells control myeloid infection. GC colonization and protective, lytic antigen-specific CD4+ T cells are now evident also for EBV. Subunit vaccines have protected only transiently against MuHV-4, but whole virus vaccines give long-term protection, via CD4+ T cells and antibody. They block infection transfer to B cells, and need include no known viral latency gene, nor any MuHV-4-specific gene. Thus, the Doherty approach of in vivo murine analysis has led to a plausible vaccine strategy for EBV and, perhaps, some insight into what CD8+ T cells really do.

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<![CDATA[Peter's Paradigm and Pandemic Preparedness]]> https://www.researchpad.co/article/Naf7b91d9-8e36-4752-8dc8-728cf07aa261 <![CDATA[Slowing Influenza Virus Evolution: A Role for Multiple Synergistic Antiviral Specificities in Vaccination Strategies]]> https://www.researchpad.co/article/Nf7005f42-533b-4650-b17f-fdbf3843241c <![CDATA[How Basic Immunological Principles May Instruct the Design of a Successful HIV-Type 1 Vaccine]]> https://www.researchpad.co/article/N134dfc66-b4da-4cde-98ff-6731b99655a7 This article is dedicated to Dr. Peter Doherty. While Peter continues to make groundbreaking discoveries in the field of immunology, he also provides outstanding scientific mentorship to his trainees. Here we contemplate our past training with Peter, Peter's teachings of basic immunological principles, and how basic principles may instruct the design of a successful human immunodeficiency virus-type 1 vaccine.

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