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

Authors

Qingsheng Li, University of MinnesotaFollow
Pamela J. Skinner, University of MinnesotaFollow
Sang-Jun Ha, Emory University School of Medicine
Lijie Duan, University of MinnesotaFollow
Teresa L. Mattila, University of Minnesota
Aaron Hage, University of Minnesota
Cara White, University of Minnesota
Daniel L. Barber, National Institute of Allergy and Infectious Diseases
Leigh O'Mara, Emory University School of Medicine
Peter J. Southern, University of Minnesota
Cavan S. Reilly, University of MinnesotaFollow
John V. Carlis, University of Minnesota
Christopher J. Miller, University of California - Davis
Rafi Ahmed, Emory University School of Medicine
Ashley T. Haase, University of MinnesotaFollow

Date of this Version

3-27-2009

Document Type

Article

Citation

Science Vol 323 27 March 2009

Comments

U.S. Government Work

Abstract

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.