Recombinant CD40L Treatment Protects Allogeneic Murine Bone Marrow Transplant Recipients From Death Caused by Herpes Simplex Virus-1 Infection |
| |
Authors: | Beland Janice L; Adler Heiko; Del-Pan Nadia C; Kozlow Wende; Sung Janice; Fanslow William; Rimm Ilonna J |
| |
Institution: | From the Department of Pediatric Oncology, Dana-Farber CancerInstitute and Children's Hospital, Harvard Medical School, Boston, MA;and Immunex, Seattle WA. |
| |
Abstract: | Posttransplant infection associated with host immune deficiency isthe major cause of nonrelapse mortality of human bone marrow transplantrecipients. In a new murine model of posttransplant infection,allogeneic bone marrow transplant recipients were infected with herpessimplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks aftertransplantation. Allogeneic transplant recipients withgraft-versus-host disease (GVHD) had significantly increased mortalityfrom HSV-1 encephalitis, with deficiencies of both specific anti-HSV-1antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokineprofile (increased interleukin-4 IL-4] and decreased interferon-)and decreased lipopolysaccharide (LPS) responses, suggesting that bothT-cell and B-cell defects contributed to the impaired production ofantibody. Because passive transfer of hyperimmune serum protected micefrom HSV-1 infection, we hypothesized that CD40 ligand (CD40L), whichinduces B-cell maturation, would protect mice from HSV-1 infection.CD40L-treated GVHD mice showed elevated IgG2a levels and increasedsurvival compared with vehicle-treated transplant recipients. |
| |
Keywords: | |
|
| 点击此处可从《Blood》浏览原始摘要信息 |
| 点击此处可从《Blood》下载免费的PDF全文 |
|