Virus-Induced Abrogation of Transplantation Tolerance Induced by Donor-Specific Transfusion and Anti-CD154 Antibody

• DOI: 10.1128/jvi.74.5.2210-2218.2000
• Publication Date: 2002-07-27T10:06:37Z
• Authors: Raymond M. Welsh; Thomas G. Markees; Bruce A. Woda; Keith A. Daniels; Michael A. Brehm; John P. Mordes; Dale L. Greiner; Aldo A. Rossini
• Keywords: CD154

ABSTRACT Treatment with a 2-week course of anti-CD154 antibody and single transfusion donor leukocytes (a donor-specific or DST) permits skin allografts to survive for >100 days in thymectomized mice. As clinical trials this methodology humans are contemplated, concern has been expressed that viral infection graft recipients may disrupt tolerance the allograft. We report acute lymphocytic choriomeningitis virus (LCMV) induced allograft rejection mice treated DST if inoculated shortly after transplantation. Isografts resisted LCMV-induced rejection, interferon-inducing agent polyinosinic:polycytidylic acid did not induce suggesting effect LCMV is simply consequence nonspecific inflammation. Administration anti-CD8 engrafted delayed rejection. Pichinde also but murine cytomegalovirus vaccinia (VV) not. Injection ∼50 induction transplantation had minimal on subsequent survival. interfere clearance LCMV, normally nonlethal high dose VV during killed recipients. conclude tolerant state can be broken by certain infections. Clinical application protocols require patient isolation facilitate procedure protect