Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3602K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goldszmid, R. S. Articles by Sher, A. Search for Related Content PubMed PubMed Citation Articles by Goldszmid, R. S. Articles by Sher, A. Social Bookmarking                            What's this?

TAP-1 indirectly regulates CD4⁺ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN- production

¹ Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
² Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702
³ Division of Immunology, Department of Microbiology and Parasitology, Federal University of Santa Catarina, Florianopolis, SC, 88040-900, Brazil

CORRESPONDENCE Romina S. Goldszmid: rgoldszmid{at}niaid.nih.gov

To investigate if transporter associated with antigen processing (TAP)–1 is required for CD8⁺ T cell–mediated control of Toxoplasma gondii in vivo, we compared the resistance of TAP-1^–/–, CD8^–/–, and wild-type (WT) mice to infection with the parasite. Unexpectedly, TAP-1^–/– mice displayed greater susceptibility than CD8^–/–, ß₂-microglobulin^–/– (ß₂m^–/–), or WT mice to infection with an avirulent parasite strain. The decreased resistance of the TAP-1^–/– mice correlated with a reduction in the frequency of activated (CD62L^low CD44^hi) and interferon (IFN)-–producing CD4⁺ T cells. Interestingly, infected TAP-1^–/– mice also showed reduced numbers of IFN-–producing natural killer (NK) cells relative to WT, CD8^–/–, or ß₂m^–/– mice, and after NK cell depletion both CD8^–/– and WT mice succumbed to infection with the same kinetics as TAP-1^–/– animals and displayed impaired CD4⁺ T cell IFN- responses. Moreover, adoptive transfer of NK cells obtained from IFN-^+/+, but not IFN-^–/–, animals restored the CD4⁺ T cell response of infected TAP-1^–/– mice to normal levels. These results reveal a role for TAP-1 in the induction of IFN-–producing NK cells and demonstrate that NK cell licensing can influence host resistance to infection through its effect on cytokine production in addition to its role in cytotoxicity.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Larrea, E., Aldabe, R., Gonzalez, I., Segura, V., Sarobe, P., Echeverria, I., Prieto, J. (2009). Oncostatin M Enhances the Antiviral Effects of Type I Interferon and Activates Immunostimulatory Functions in Liver Epithelial Cells. J. Virol. 83: 3298-3311 [Abstract] [Full Text]  
• Kalkunte, S. S., Mselle, T. F., Norris, W. E., Wira, C. R., Sentman, C. L., Sharma, S. (2009). Vascular Endothelial Growth Factor C Facilitates Immune Tolerance and Endovascular Activity of Human Uterine NK Cells at the Maternal-Fetal Interface. J. Immunol. 182: 4085-4092 [Abstract] [Full Text]  
• Goldszmid, R. S., Coppens, I., Lev, A., Caspar, P., Mellman, I., Sher, A. (2009). Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells. JEM 206: 399-410 [Abstract] [Full Text]  
• Winkler-Pickett, R., Young, H. A., Cherry, J. M., Diehl, J., Wine, J., Back, T., Bere, W. E., Mason, A. T., Ortaldo, J. R. (2008). In Vivo Regulation of Experimental Autoimmune Encephalomyelitis by NK Cells: Alteration of Primary Adaptive Responses. J. Immunol. 180: 4495-4506 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS