The Histology Core will provide support for histological and immunological staining of tissue samples from Projects 1-4. Appropriately prepared tissues will be embedded in paraffin or OCT for sectioning and staining. Routine histological stains will be performed. Single or 2-color immunohistochemical staining will be performed with the ABC method. For immunofluorescence, either fixed or frozen sections will be stained by Ab against lineage-specific markers for leukocyte populations, or surface costimulation molecules, adhesion molecules, receptors, and cytokines. Up to 4 color immunoflourescence staining will be performed for confocal microscopy analysis. The Histology core will also develop new reagents for studying effector cell function and development during virus infections and work closely with the Flow Cytometry Core to define Ab staining conditions and marker expression by leukocytes during virus infection. The usage of the core by the 4 projects are as follows: Project 1: Staining of mouse lung and lymph node tissues for inflammation, infiltrating cell population, and the expression of cytokine and surface receptors by CD8+ T cells, NK cells, dendritic cells, and other hematopoietic cells during influenza virus infection. Project 2: Staining of mouse liver cells for infiltrating leukocyte populations and their Ag expression and cytokine production during adenovirus infection;Reagents to block the interaction of CD8+ T cells with NK cells, dendritic cells and other cell types will be developed by the Core. Project 3: Spleen sections staining for infiltrating cells, cytokine production, and CD8+ T cell interaction with NK cells and dendritic cells during MCMV infection in susceptible and resistant mouse strains. Project 4: Staining of mouse lung and lymphoid tissues for infiltrating leukocyte subsets, surface molecules, and cytokines during influenza infection and blocking of CD8+ T cell interaction with accessory cells. The long term aim of the core is to provide support for the acquisition of immunological information on CD8+ effector cell development and function in viral infections and the influences of other cell types on CD8+ T cell functions.

Public Health Relevance

Immunohistochemical and immunofluorescence studies of target and lymphoid tissues will provide important information on the pathogenesis, cellular interactions, and effector cell functions of target organs during virus infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-BDP-I)
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University of Virginia
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Dolina, Joseph S; Braciale, Thomas J; Hahn, Young S (2014) Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9-independent T-cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice. Hepatology 59:1351-65
Moser, Emily K; Hufford, Matthew M; Braciale, Thomas J (2014) Late engagement of CD86 after influenza virus clearance promotes recovery in a FoxP3+ regulatory T cell dependent manner. PLoS Pathog 10:e1004315
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DeBerge, Matthew P; Ely, Kenneth H; Enelow, Richard I (2014) Soluble, but not transmembrane, TNF-? is required during influenza infection to limit the magnitude of immune responses and the extent of immunopathology. J Immunol 192:5839-51
Kim, Taeg S; Gorski, Stacey A; Hahn, Steven et al. (2014) Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism. Immunity 40:400-13
Yoo, Jae-Kwang; Braciale, Thomas J (2014) IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection. PLoS One 9:e105872
Yoo, Jae-Kwang; Kim, Taeg S; Hufford, Matthew M et al. (2013) Viral infection of the lung: host response and sequelae. J Allergy Clin Immunol 132:1263-76; quiz 1277
Braciale, Thomas J; Hahn, Young S (2013) Immunity to viruses. Immunol Rev 255:5-12
Gorski, Stacey Ann; Hahn, Young S; Braciale, Thomas J (2013) Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection. PLoS Pathog 9:e1003615
Goh, Celeste; Narayanan, Sowmya; Hahn, Young S (2013) Myeloid-derived suppressor cells: the dark knight or the joker in viral infections? Immunol Rev 255:210-21

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