Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4472-4478
Recombinant CD40L Treatment Protects Allogeneic Murine Bone Marrow
Transplant Recipients From Death Caused by Herpes Simplex Virus-1
Infection
Janice L. Beland,
Heiko Adler,
Nadia C. Del-Pan,
Wende Kozlow,
Janice Sung,
William Fanslow, and
Ilonna J. Rimm
From the Department of Pediatric Oncology, Dana-Farber Cancer
Institute and Children's Hospital, Harvard Medical School, Boston, MA;
and Immunex, Seattle WA.
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-
)
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.
