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Influenza Virus and Poly(I:C) Inhibit MHC Class I-Restricted Presentation of Cell-Associated Antigens Derived from Infected Dead Cells Captured by Human Dendritic Cells¹

Baylor-National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, Texas 75204

During viral infection, dendritic cells (DCs) capture infected cells and present viral Ags to CD8⁺ T cells. However, activated DCs might potentially present cell-associated Ags derived from captured dead cells. In this study, we find that human DCs that captured dead cells containing the TLR3 agonist poly(I:C) produced cytokines and underwent maturation, but failed to elicit autologous CD8⁺ T cell responses against Ags of dead cells. Accordingly, DCs that captured dead cells containing poly(I:C), or influenza virus, are unable to activate CD8⁺ T cell clones specific to cell-associated Ags of captured dead cells. CD4⁺ T cells are expanded with DCs that have captured poly(I:C)-containing dead cells, indicating the inhibition is specific for MHC class I-restricted cross-presentation. Furthermore, these DCs can expand naive allogeneic CD8⁺ T cells. Finally, soluble or targeted Ag is presented when coloaded onto DCs that have captured poly(I:C)-containing dead cells, indicating the inhibition is specific for dead cell cargo that is accompanied by viral or poly(I:C) stimulus. Thus, DCs have a mechanism that prevents MHC class I-restricted cross-presentation of cell-associated Ag when they have captured dead infected cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Baylor Health Care Systems Foundation, the National Institutes of Health (U19 AIO57234, P01 CA84512, R0-1 CA78846 and CA85540 to J.B.). J.B. holds the Caruth Chair for Transplantation Immunology Research. A.K.P. holds the Ramsay Chair for Cancer Immunology Research.

² Address correspondence and reprint requests to Dr. A. Karolina Palucka, Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204. E-mail address: karolinp{at}baylorhealth.edu

³ Abbreviations used in this paper: DC, dendritic cell; CTL, cytotoxic T lymphocyte; BA, betulinic acid; FluM1, influenza A virus M1; DCIR, DC immunoreceptor.

⁴ The online version of this article contains supplementary material.