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Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 12/27/2011, Vol. 108 Issue 52, p21182-21187, 6p
- Publication Year :
- 2011
-
Abstract
- CD4 T cells play a critical role in regulating CD8 T-cell responses during chronic viral infection. Several studies in animal models and humans have shown that the absence of CD4 T-cell help results in severe dysfunction of virus-specific CD8 T cells. However, whether function can be restored in already exhausted CD8 T cells by providing CD4 T-cell help at a later time remains unexplored. In this study, we used a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Adoptive transfer of LCMV-specific CD4 T cells into chronically infected mice restored proliferation and cytokine production by exhausted virus-specific CD8 T cells and reduced viral burden. Although the transferred CD4 T cells were able to enhance function in exhausted CD8 T cells, these CD4 T cells expressed high levels of the programmed cell death (PD)-1 inhibitory receptor. Blockade of the PD-1 pathway increased the ability of transferred LCMV-specific CD4 T cells to produce effector cytokines, improved rescue of exhausted CD8 T cells, and resulted in a striking reduction in viral load. These results suggest that CD4 T-cell immunotherapy alone or in conjunction with blockade of inhibitory receptors may be a promising approach for treating CD8 T-cell dysfunction in chronic infections and cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- CD4 antigen
CD8 antigen
VIRUS diseases
T cells
LYMPHOCYTIC choriomeningitis virus
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 108
- Issue :
- 52
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 70146417
- Full Text :
- https://doi.org/10.1073/pnas.1118450109