Clinical and Developmental Immunology
Volume 2007 (2007), Article ID 93462, 9 pages
doi:10.1155/2007/93462
Research Article

Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

Maria S. Salvato,1 C. Cameron Yin,2,3 Hideo Yagita,4 Toshihiro Maeda,5 Ko Okumura,5 Ilia Tikhonov,1 and C. David Pauza1

1Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore 21201, MD, USA
2Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison 53705, WI, USA
3Department of Hematopathology, MD Anderson Cancer Center, University of Texas, Houston 77030, TX, USA
4Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
5The Chemo-Sero Therapeutic Research Institute (Kaketsuken), Kumamoto 860-8568, Japan

Received 8 October 2007; Accepted 31 October 2007

Academic Editor: Ethan M. Shevach

Copyright © 2007 Maria S. Salvato et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander) cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203). Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.