Recombinant CD40L Treatment Protects Allogeneic Murine Bone Marrow Transplant Recipients From Death Caused by Herpes Simplex Virus-1 Infection

Author:

Beland Janice L.1,Adler Heiko1,Del-Pan Nadia C.1,Kozlow Wende1,Sung Janice1,Fanslow William1,Rimm Ilonna J.1

Affiliation:

1. From the Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Harvard Medical School, Boston, MA; and Immunex, Seattle WA.

Abstract

Abstract Posttransplant infection associated with host immune deficiency is the major cause of nonrelapse mortality of human bone marrow transplant recipients. In a new murine model of posttransplant infection, allogeneic bone marrow transplant recipients were infected with herpes simplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks after transplantation. Allogeneic transplant recipients with graft-versus-host disease (GVHD) had significantly increased mortality from HSV-1 encephalitis, with deficiencies of both specific anti–HSV-1 antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokine profile (increased interleukin-4 [IL-4] and decreased interferon-γ) and decreased lipopolysaccharide (LPS) responses, suggesting that both T-cell and B-cell defects contributed to the impaired production of antibody. Because passive transfer of hyperimmune serum protected mice from HSV-1 infection, we hypothesized that CD40 ligand (CD40L), which induces B-cell maturation, would protect mice from HSV-1 infection. CD40L-treated GVHD mice showed elevated IgG2a levels and increased survival compared with vehicle-treated transplant recipients.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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