Case report Suppression of cell-mediated immunity by a donor-transmitted lymphocytic choriomeningitis virus in a kidney transplant recipient Amitabh Gautam 1,2 , S.A. Fischer 1,3 , A.F. Yango 1,4 , R.Y. Gohh 1,4 , P.E. Morrissey 1,2 , A.P. Monaco 1,2 1 Division of Organ Transplantation, Rhode Island Hospital, 2 Department of Surgery, 3 Department of Medicine (Division of Infectious Diseases), 4 Department of Medicine (Division of Nephrology), Brown Medical School, Providence, Rhode Island, USA A. Gautam, S.A. F|scher, A.F.Yango, R.Y. Gohh, P.E. Morrissey, A.P. Monaco. Suppression ofcell-mediated immunityby adonor-transmitted lymphocytic choriomeningitis virus in a kidney transplant recipient. Transpl Infect Dis 2007. All rights reserved Abstract: Infectionwith lymphocytic choriomeningitis virus (LCMV) in rodents, the primary host, is known to cause suppression of cell- mediated immunity. Serial determinations using a functional cell- mediated immune assay in a kidney transplant recipient with donor- transmitted LCMValso suggested profound suppression of cellular immunity.This suppression persisted in spite of reduction of immunosuppression.W|th the clearance of the virus there was reconstitution of the cellular immune response.                                                                                       The interaction between viral infections and the human immune system is complex. Cell-mediated immunity is important for viral control and clearance after infection. Many viruses, however, can cause a suppression of cell- mediated immunity on initial infection. Drug-induced immunosuppression in organ transplantation recipients adds further complexity to this interaction. In May 2005 lymphocytic choriomeningitis virus (LCMV) was transmitted from an organ donor to 4 recipi- ents (2 kidney, 1 each lung and liver). All, except one of the kidney recipients, had a fatal outcome (1). We have been clinically evaluating a US Food and Drug Administration (FDA)-approved assay (Immuknowt, Cy- lex Inc., Columbia, Maryland, USA) to quantifycell-medi- ated immunity in recipients of kidney and pancreas transplantation on chronic immunosuppression.The test is performed on whole blood, which is incubated over- night for 15^18h with phytohemagglutinin as a stimu- lant. Anti-CD4 monoclonal antibody-coated magnetic beads are added after incubation to select CD4 1 cells and a lysing agent is added to these cells to release intra- cellular adenosine triphosphate (ATP). A luminescent re- agent (luciferin/luciferase) is added to the cell lysate and, within 30 min, light emitted is measured by a luminome- ter. The amount of light produced is proportional to the concentration of ATP.The concentration of ATP (ng/mL) is calculated from a calibration curve. Based on initial multicenter studies (2) on healthy adults and transplant recipients, it was suggested that the immune cell re- sponse could be divided into low ( o225 ATP ng/mL), moderate (226^524 ATP ng/mL), and high ( 4525 ATP ng/mL). This test was used serially during the manage- ment of the surviving recipient of donor-transmitted in- fection with LCMV. The results suggest that the LCMV caused profound early depression of cell-mediated immu- nity in the human host. Copyright r Blackwell Munksgaard 2007 Transplant Infectious Disease . ISSN 1398-2273 Key words: lymphocytic choriomeningitis virus; cellular immunity; immunologic monitoring; kidney transplantation; CD4-positive T lymphocytes Correspondence to: Amitabh Gautam, MD, APC 921, Rhode Island Hospital, Providence, RI 02903, USA Tel: 1 1 401 444 5285 Fax: 1 1 401 444 3283 E-mail: agautam@lifespan.org Received 30 October 2006, revised 15 December 2006, accepted for publication 18 December 2006 DOI: 10.1111/j.1399-3062.2007.00232.x Transpl Infect Dis 2007 1