The Journal of Immunology, 2007, 178: 46.10.
Copyright © 2007 by The American Association of Immunologists, Inc.
Functionally impaired T cell-dependent immunopathology in FK506-treated mice with LCMV infection
Koichi Araki1,
Shivaprakash Gangappa2,
Barry T Rouse3,
Christian P Larsen2 and
Rafi Ahmed1
1 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Road, Atlanta, GA, 30322,
2 Emory Transplant Center, Department of Surgery, Emory University School of Medicine, 101 Woodruff Circle, Suite 5105, Atlanta, GA, 30322,
3 Department of Microbiology and Pathobiology, College of Veterinary Medicine, University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996
Abstract
Lymphocytic choriomeningitis virus (LCMV) was recently shown to contaminate transplanted organs with lethal consequences in transplant recipients. The diagnosis of LCMV as a cause of death under circumstances of immunosuppression is somewhat paradoxical since LCMV is a non-cytolytic virus and is the classic example of immune-mediated disease. To understand how treatment with immunosuppressive drugs given to transplant recipients results in LCMV disease, we have initiated studies using the calcineurin inhibitor FK506. Surprisingly, FK506-treated LCMV-infected mice showed high lethality. The drug treatment resulted in a failure of infection control and interestingly induced functionally impaired virus-specific T cells. Lesions and death appeared to be the consequence of overproduction of cytokines, such as TNF-alpha. This response was dependent on the presence of T cells but these cells themselves appeared not to be the source of the disease-producing cytokines. Our results suggest that functionally impaired T cells in drug treated animals signal cells in LCMV infected tissues to overproduce the cytokines responsible for lesions.
