In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 74.4-74.4
Abstract:
T-bet induced CD4+ T cells are committed to be IFN-γ competent Th1 cells. The Th1 response is essential for virus eradication, but is also a major cause of inflammation and disease aggravation in severe influenza. In our influenza hemagglutinin (HA) Ag-specific mouse experimental system, naïve CD4+ T cells respond to the infection with T-bet expression. However, they suppress cognate CD8+ T cell effector response-mediated inflammation and alleviate the disease. Here we report concomitant LAG-3 expression and IFN-γ competence in Th1 committed CD4+ T cells. LAG-3 expression increases with activation by virus as revealed by CFSE based cell division study. The Th1 committed cells with moderate LAG-3 expression produce IFN-γ and contribute to inflammation and aggravated disease. They can no longer produce IFN-γ with higher LAG-3 expression upon further activation. Th1 committed CD4+ T cells with high LAG-3 expression suppress cognate CD8+ T cells by decoupling their effector function from proliferative response, restrain lung inflammation and facilitate viral clearance. They are better than Foxp-3+HA-specific CD4+ T cells in disease amelioration. The Foxp-3+ cells suppress both effector function and proliferative response of CD8+ T cells. They moderate inflammation but impair viral clearance. Principal component analysis of genome-wide gene expression profiles further confirmed the stepwise evolution. Several regulatory function-associated genes such as Lag3, Pdcd1, Tigit, Ctla2a, Nr4a2, Klrc1, Rgs16, Sytl3, Il21, Il1r2 and Dusp4 are up-regulated graduallly as well from LAG-3Neg to LAG-3Med and LAG-3High cells.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.74.4
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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