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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.<\/jats:p>","DOI":"10.1073\/pnas.1118450109","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T00:15:49Z","timestamp":1323735349000},"page":"21182-21187","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":174,"title":["Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection"],"prefix":"10.1073","volume":"108","author":[{"given":"Rachael D.","family":"Aubert","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice O.","family":"Kamphorst","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surojit","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaiva","family":"Vezys","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Jun","family":"Ha","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Barber","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilin","family":"Ye","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene H.","family":"Sharpe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; 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