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Science 27 March 2009:
Vol. 323. no. 5922, pp. 1726 - 1729
DOI: 10.1126/science.1168676
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Reports

Visualizing Antigen-Specific and Infected Cells in Situ Predicts Outcomes in Early Viral Infection

Qingsheng Li,1 Pamela J. Skinner,2 Sang-Jun Ha,3 Lijie Duan,1 Teresa L. Mattila,2 Aaron Hage,2 Cara White,2 Daniel L. Barber,4 Leigh O'Mara,3 Peter J. Southern,1 Cavan S. Reilly,5 John V. Carlis,6 Christopher J. Miller,7 Rafi Ahmed,3 Ashley T. Haase1*

In the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. We combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. In simian immunodeficiency virus infections in macaques and lymphocytic choriomeningitis virus infections in mice, the magnitude and timing of the establishment of an excess of effector cells versus targets were found to correlate with the extent of control and the infection outcome (i.e., control and clearance versus partial or poor control and persistent infection). This method highlights the importance of the location, timing, and magnitude of the immune response needed for a vaccine to be effective against agents of persistent infection, such as HIV-1.

1 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
2 Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN55108, USA.
3 Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
4 Immunobiology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
5 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
6 Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, Minneapolis, MN 55455, USA.
7 Center for Comparative Medicine, California National Primate Research Center, University of California, Davis, CA 95616, USA.

* To whom correspondence should be addressed. E-mail: haase001{at}umn.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)