Abstract

The proposal investigates the interplay of host and viral factors involved in the development of the immune response to Respiratory Syncitial Virus (RSV) infection in mice. Preliminary data indicate that RSV-specific CD8+ T lymphocytes play an important regulatory role in directing the differentiation of RSV-specific memory CD4+ T lymphocytes into Th-1 or Th-2 effectors.
In Aim 1, an in vitro model will be developed to investigate the role of CD8+ T cells in the development of effector CD4+ T cells. In particular, the roles of soluble and cell associated CD8 T lymphocyte gene products in driving Th-1 versus Th-2 responses to the RSV-G glycoprotein will be investigated.
In Aim 2, subdominant Th epitopes will be identified to examine their contribution to Th-2 effector function and pulmonary eosinophil accumulation in response to RSV challenge. Finally in Aim 3, a combination of selective breeding and chromosomal DNA marker analysis will be used to identify host genetic loci that regulate the response of CD4+ T lymphocytes to RSV infection. These studies will provide new and potentially important information on the interaction of CD4+ and CD8+ T cells in the clearance of RSV infection. This information will be important for the development of an effective RSV vaccine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037293-07
Application #
6170046
Study Section
Virology Study Section (VR)
Program Officer
Rubin, Fran A
Project Start
1994-09-30
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
7
Fiscal Year
2000
Total Cost
$266,419
Indirect Cost

  Institution

Name
University of Virginia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Moser, Emily K; Sun, Jie; Kim, Taeg S et al. (2015) IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after Influenza A virus infection. PLoS One 10:e0120169
Yao, S; Jiang, L; Moser, E K et al. (2015) Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection. Mucosal Immunol 8:746-59
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
Varga, Steven M; Braciale, Thomas J (2013) The adaptive immune response to respiratory syncytial virus. Curr Top Microbiol Immunol 372:155-71
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
Sun, Jie; Braciale, Thomas J (2013) Role of T cell immunity in recovery from influenza virus infection. Curr Opin Virol 3:425-9
Hufford, Matthew M; Richardson, Graham; Zhou, Haixia et al. (2012) Influenza-infected neutrophils within the infected lungs act as antigen presenting cells for anti-viral CD8(+) T cells. PLoS One 7:e46581
Yoo, Jae-Kwang; Fish, Eleanor N; Braciale, Thomas J (2012) LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells during respiratory virus infection. J Exp Med 209:1853-67
Gorski, Stacey A; Hufford, Matthew M; Braciale, Thomas J (2012) Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract. Curr Opin Virol 2:233-41
Braciale, Thomas J; Sun, Jie; Kim, Taeg S (2012) Regulating the adaptive immune response to respiratory virus infection. Nat Rev Immunol 12:295-305

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