Differentiation of CD4 T cells into functionally distinct effector subsets has been intensively studied in vitro and the subset-specific roles of CD4 T cells have been also considered important in vivo. TH1 CD4 T cells, which express T-bet and IFN-?, are thought to be important for both adaptive and innate immune responses to infection by intracellular pathogens and cancers. However, since T-bet is expressed in both CD4 and CD8 T cells, and IFN-? is expressed by other cell populations, such as CD8 T cells and NK cells, the conventional conditional knockout or germline knockout approaches have failed to specifically demonstrate the requirement for TH1 cells in vivo. To address this fundamental question, we have developed a new genetic tool and will define the roles of TH1 cells in vivo using viral infection models.

Public Health Relevance

CD4 T cell differentiation to effector subsets has been studied intensively in vitro and also considered to be important in vivo. Yet, the in vivo roles, particularly those of TH1 cells, have not been rigorously tested due to technical limitations. In this proposed study, we will use our newly developed Cre driver to determine whether TH1 differentiation is required for adaptive immune responses to viral infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI139875-01
Application #
9585530
Study Section
Cellular and Molecular Immunology - A Study Section (CMIA)
Program Officer
Ramachandra, Lakshmi
Project Start
2018-05-07
Project End
2020-04-30
Budget Start
2018-05-07
Budget End
2019-04-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Washington University
Department
Pathology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130