Viral ImmunologyVol. 29, No. 4 EditorialInfluenza VaccinesDavid L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:4 May 2016https://doi.org/10.1089/vim.2016.29008.dlwAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Influenza Vaccines." Viral Immunology, 29(4), p. 197FiguresReferencesRelatedDetails Volume 29Issue 4May 2016 InformationCopyright 2016, Mary Ann Liebert, Inc.To cite this article:David L. Woodland.Influenza Vaccines.Viral Immunology.May 2016.197-197.http://doi.org/10.1089/vim.2016.29008.dlwPublished in Volume: 29 Issue 4: May 4, 2016Online Ahead of Print:April 20, 2016PDF download

Viral ImmunologyVol. 26, No. 4 EditorialFactors that Control Susceptibility to Theiler's Murine Encephalomyelitis VirusDavid L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:13 Aug 2013https://doi.org/10.1089/vim.2013.ed.26.4AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail View article"Factors that Control Susceptibility to Theiler's Murine Encephalomyelitis Virus." , 26(4), pp. 221–222FiguresReferencesRelatedDetails Volume 26Issue 4Aug 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:David L. Woodland.Factors that Control Susceptibility to Theiler's Murine Encephalomyelitis Virus.Viral Immunology.Aug 2013.221-222.http://doi.org/10.1089/vim.2013.ed.26.4Published in Volume: 26 Issue 4: August 13, 2013PDF download

Viral ImmunologyVol. 24, No. 1 EditorialViral Immunology in 2011David L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:14 Feb 2011https://doi.org/10.1089/vim.2011.ed.24.1AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Viral Immunology in 2011." , 24(1), p. 1FiguresReferencesRelatedDetails Volume 24Issue 1Feb 2011 InformationCopyright 2011, Mary Ann Liebert, Inc.To cite this article:David L. Woodland.Viral Immunology in 2011.Viral Immunology.Feb 2011.1-1.http://doi.org/10.1089/vim.2011.ed.24.1Published in Volume: 24 Issue 1: February 14, 2011PDF download

Viral ImmunologyVol. 23, No. 1 EditorialA Strong Start to 2010David L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:1 Feb 2010https://doi.org/10.1089/vim.2010.Editorial23.1AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleAbstractFiguresReferencesRelatedDetails Volume 23Issue 1Feb 2010 InformationCopyright 2010, Mary Ann Liebert, Inc.To cite this article:David L. Woodland.A Strong Start to 2010.Viral Immunology.Feb 2010.1-2.http://doi.org/10.1089/vim.2010.Editorial23.1Published in Volume: 23 Issue 1: February 1, 2010PDF download

Effector T cells are a crucial component of the adaptive immune response to respiratory virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of respiratory virus-specific CD8+ T cells, it is unclear whether these receptors govern effector CD4+ T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4+ T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4+ T cell proliferation, phenotype, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls virus-specific effector CD4+ T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during respiratory virus infections.

CD8+ T cells are a major source of IFN-γ, a key effector cytokine in immune responses against many viruses and protozoa. Although the transcription factor T-bet is required for IFN-γ expression in CD4+ T cells, it is reportedly dispensable in CD8+ T cells, where the transcription factor Eomesodermin is thought to be sufficient. The diverse functions of IFN-γ are mediated through the IFN-γR and STAT1. In CD4+ T cells, STAT1 appears to be critical for the activation of T-bet and IFN-γ, suggesting an IFN-γ-dependent positive feedback loop. However, STAT1 can also be activated by other cytokines, including IL-27. In the present study we show that, in contrast to in vitro conditions and the prevailing paradigm, T-bet is critical for the in vivo IFN-γ production by CD8+ T cells upon infection of mice with diverse pathogens. Whereas IFN-γR signals are dispensable for the T-bet-dependent IFN-γ production, direct IL-27Rα signals are critical.

The tuberculin skin test (TST) reaction depends on the presence and function of T lymphocytes. However it is still unclear whether numbers of T-cells or their ability to secrete interferon-gamma (IFN-g) are key to determine a TST reaction.

Viral ImmunologyVol. 20, No. 3 EditorialRising ImpactDavid L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:11 Oct 2007https://doi.org/10.1089/vim.2007.9991AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Rising Impact." , 20(3), pp. 329–330FiguresReferencesRelatedDetails Volume 20Issue 3Sep 2007 InformationMary Ann Liebert, Inc.To cite this article:David L. Woodland.Rising Impact.Viral Immunology.Sep 2007.329-330.http://doi.org/10.1089/vim.2007.9991Published in Volume: 20 Issue 3: October 11, 2007PDF download

Respiratory virus infections establish a population of memory CD8+ T cells in the lung airways that persist for months after infection. However, the relationship between Ag-specific memory T cells in the lung airways and the systemic memory T cell pool is not well understood. The majority of lung airway memory T cells express a highly activated phenotype (CD69+/CD127−), suggesting that recent Ag stimulation is required to drive T cell activation and recruitment to the lung airways. In this study, we demonstrate that the lung airway environment itself in the absence of cognate Ag alters the expression of acute activation markers such as CD69 and CD127 on memory CD8+ T cells. Furthermore, the steady-state recruitment of virus-specific memory CD8+ T cells to the lung airways from the circulation can occur without recent Ag stimulation. These findings alter the current perceptions concerning the contribution of Ag to the maintenance of peripheral T cell memory.

Viral ImmunologyVol. 20, No. 4 EditorialAnother Strong IssueDavid L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:25 Dec 2007https://doi.org/10.1089/vim.2007.ED20.4AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetails Volume 20Issue 4Dec 2007 InformationMary Ann Liebert, Inc.To cite this article:David L. Woodland.Another Strong Issue.Viral Immunology.Dec 2007.503-504.http://doi.org/10.1089/vim.2007.ED20.4Published in Volume: 20 Issue 4: December 25, 2007PDF download

Increasing age is associated with the development of CD8+ T cell clonal expansions (TCE) that can dominate the peripheral T cell repertoire and interfere with immune responses to infection and vaccination. Some TCE are driven by chronic infections, consistent with dysregulated outgrowth of T cell clones in response to persistent antigenic stimulation. However, a second class of TCE develops with age in the absence of chronic infections and is poorly understood in terms of origin or Ag dependence. In this study, we present evidence that Ag-specific TCE develop at high frequencies from conventional memory CD8+ T cell pools elicited by nonpersistent influenza and parainfluenza virus infections. Putative TCE occurred in both the central- and effector-memory CD8+ T cell populations and did not require Ag for their maintenance. In addition, they were similar to normal memory T cells in terms of phenotype and function, suggesting that they develop stochastically from the memory T cell pool. These data suggest that memory T cell pools become progressively dysregulated over time and this may have a significant impact on immune responsiveness in the aged.

Viral ImmunologyVol. 19, No. 4 EditorialThank You, CarolDavid L. WoodlandDavid L. WoodlandSearch for more papers by this authorPublished Online:4 Jan 2007https://doi.org/10.1089/vim.2006.19.591AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Thank You, Carol." , 19(4), pp. 591–592FiguresReferencesRelatedDetails Volume 19Issue 4Dec 2006 InformationCopyright 2006, Mary Ann Liebert, Inc.To cite this article:David L. Woodland.Thank You, Carol.Viral Immunology.Dec 2006.591-592.http://doi.org/10.1089/vim.2006.19.591Published in Volume: 19 Issue 4: January 4, 2007PDF download

The murine γ-herpesvirus-68 (γHV68) establishes viral latency in dendritic cells (DCs). In the present study, we examined the specific consequences of DC infection by γHV68, both in vivo and in vitro. Ex vivo analysis of infected mice showed that the virus colonizes respiratory DCs very early after infection and that all subsets of splenic DCs analyzed are viral targets. We have developed and characterized an in vitro model of γHV68 infection of DCs. Using this model, we demonstrated that viral infection neither induces full DC maturation nor interferes with exogenous activation, which is assessed by cell surface phenotypic changes. However, whereas γHV68 infection alone failed to elicit cytokine secretion, IL-10 secretion of exogenously activated DCs was enhanced. Furthermore, γHV68-infected DCs efficiently stimulated virus-specific T cell hybridomas but failed to induce alloreactive stimulation of normal T cells. These data indicate that viral infection doesn’t interfere with Ag processing and presentation but does interfere with the ability of DCs to activate T cells. The inhibition of T cell activation was partially reversed by blocking IL-10. Analysis of infected mice shows elevated levels of IL-10 expression in DCs and that lack of endogenous IL-10 is associated with decreased γHV68 long-term latency. Taken together, these observations indicate that γ2-herpesvirus infection of DCs is a mechanism of viral immune evasion, partially mediated by IL-10.

The expression of IFN-γ is a hallmark of Th1 cells and CD8+ effector T cells and is the signature cytokine of type 1 responses. However, it is not known whether T cells are homogeneous in their capacity to produce IFN-γ, whether this potential varies between tissues, and how it relates to the production of other effector molecules. In the present study we used bicistronic IFN-γ-enhanced yellow fluorescent protein (IFN-γ-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-γ expression at the single cell level. The eYFP fluorescence of Th1 cells and CD8+ effector T cells was broadly heterogeneous even before cell division and correlated with both the abundance of IFN-γ transcripts and the secretion of IFN-γ upon stimulation. CD4+ and CD8+ T cells of influenza-infected mice revealed a similarly heterogeneous IFN-γ expression, and eYFPhigh cells were only found in the infected lung. Ag-specific T cells were in all examined tissues eYFP+, but also heterogeneous in their reporter fluorescence, and eYFPhigh cells were also restricted to the infected lung. A similar heterogeneity was observed in Toxoplasma gondii-infected animals, but eYFPhigh cells were restricted to different tissues. Highly eYFP fluorescent cells produced elevated levels of proinflammatory cytokines and chemokines in addition to IFN-γ, suggesting their coregulated expression as a functional unit in highly differentiated effector T cells.

The relative contributions of CD62Lhigh (central) memory and CD62Llow (effector) memory T cell populations to recall responses are poorly understood, especially in the respiratory tract. In this study, we took advantage of a dual-adoptive transfer system in the mouse to simultaneously follow the recall response of effector and central memory subpopulations to intranasal parainfluenza virus infection. Using MHC class I and class II multimers, we tracked the responses of Ag-specific CD8+ and CD4+ memory T cells in the same animals. The data show that effector memory T cells mounted recall responses that were equal to, or greater than, those mounted by central memory T cells. Moreover, effector memory T cells were more efficient at subsequently establishing a second generation of memory T cells. These data contrast with other studies indicating that central memory CD8+ T cells are the prominent contributors to systemic virus infections.

Lymphocyte activation gene-3 (LAG-3) is a CD4-related, activation-induced cell surface molecule that binds to MHC class II with high affinity. In this study, we used four experimental systems to reevaluate previous suggestions that LAG-3−/− mice had no T cell defect. First, LAG-3−/− T cells exhibited a delay in cell cycle arrest following in vivo stimulation with the superantigen staphylococcal enterotoxin B resulting in increased T cell expansion and splenomegaly. Second, increased T cell expansion was also observed in adoptive recipients of LAG-3−/− OT-II TCR transgenic T cells following in vivo Ag stimulation. Third, infection of LAG-3−/− mice with Sendai virus resulted in increased numbers of memory CD4+ and CD8+ T cells. Fourth, CD4+ T cells exhibited a delayed expansion in LAG-3−/− mice infected with murine gammaherpesvirus. In summary, these data suggest that LAG-3 negatively regulates T cell expansion and controls the size of the memory T cell pool.