Research Lab of Jonathan Boyson, Ph.D.
Dr. Boyson's lab studies the role of iNKT and gamma delta T cell subsets in the immune response. These unusual, innate-like T cell subsets differ from conventional T cells in that they are preferentially localized to peripheral tissues, rapidly produce large amounts of cytokines upon stimulation, and influence the function of a variety of different leukocyte subsets. Innate-like T cells, therefore, are well-suited to play an important role early in the development of the immune response, and have been demonstrated to play critical roles in a variety of infectious diseases (influenza, Coxsackievirus B3, S. pneumoniae, P. aeruginosa, S. aureus, B. burgdorferi, etc.). They are especially interested in determining how genetic regulation of these innate-like T cell subsets affects host susceptibility to infectious disease.
|Oliver Dienz, Ph.D.||Research Associate||(802) 656-8836|
|Vicki DeVault||Graduate Research Assistant||(802) 656-8832|
|Nancy Graham||Laboratory Technician||(802) 656-8832|
|Natalie Nazarian||Post-baccalaureate PreMed||(802) 656-8832|
|Murisa Malagic||Undergraduate||(802) 656-8832|
Programs & Projects
A host genetic locus that regulates susceptibility to influenza infection
Susceptibility to infectious disease is one of the most strongly inherited of all common disease traits. Yet, we still do not have a clear understanding of how host genetic regulation of the immune response ultimately affects disease outcome. Slam genes comprise a family of tightly linked genes that encode costimulatory/adhesion molecules that transduce signals through association with the cytosolic adapter protein, SLAM-associated protein (SAP). Mutations in the gene encoding SAP (Sh2d1a) results in the development of a serious immunodeficiency that often results in mortality due to virus infection, highlighting the central role that the Slam/SAP signaling pathway plays in the host response to viral pathogens. Slam genes are polymorphic in humans and in mice, and these polymorphisms have been linked to the development of autoimmunity. However, despite the significant role that the Slam/SAP signaling pathway plays in the host response to virus infection, there has been almost no study of the potential contribution of Slam locus polymorphisms to susceptibility to virus infection.
We are studying the contribution of naturally occurring genetic variation at the Slam locus to host susceptibility to influenza infection. Our preliminary data indicates that one or more genes within this locus regulates susceptibility to influenza infection, and that mortality is associated with an increase in IL-17A-producing gamma delta T cells in the lung. Our working hypothesis is that genetic variation at one or more Slam genes regulates susceptibility to virus infection through regulation of gamma delta T cell and/or NKT cell function.
The function of Slamf6 on NKT cells
Slamf6 (Ly108) and Slamf1 have previously been demonstrated to be critical in NKT cell development. In mice that are only deficient in Slamf6, NKT cells develop, but there are fewer of them, and their numbers are particularly low in the liver. In addition, it has been demonstrated that the absence of NKT cells in SAP-deficient mice is due to negative signaling from the Slamf6 receptor. However, the exact nature of the function of Slamf6 on NKT cells in the periphery is still unclear. We are utilizing Slamf6-deficient mice (a gift from Pam Schwartzberg) and B6.129 congenic strains in which a 129X1/SvJ-derived region encompassing the Slam genes has been introgressed onto the C57BL/6J background to investigate this question.
Immune Correlates of protection in a candidate Dengue virus vaccine trial
Dengue virus infection constitutes a significant global health problem, and numerous efforts are underway to develop an effective vaccine. We are collaborating with Beth Kirkpatrick MD and Sean Diehl PhD in the University of Vermont Vaccine Testing Center, and Jason Botten PhD in the Dept. of Medicine to evaluate immune correlates of protection in a candidate live attenuated tetravalent vaccine developed at the NIH. Using dengue-specific MHC class I peptide pools provided by Alex Sette PhD and Daniela Weiskopf PhD at the La Jolla Institute for Allergy and Immunology (LIAI), we are evaluating the breadth and magnitude of the CD8+ and CD4+ T cell responses in a human challenge model of dengue vaccination.
Last modified August 11 2015 05:55 PM