Functionally impaired T cell-dependent immunopathology in FK506-treated mice with LCMV infection (46.10)

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.