Recombinant CD40L treatment protects allogeneic murine bone marrow transplant recipients from death caused by herpes simplex virus-1 infection.
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-gamma) 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.
Beland
J L
JL
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, MA, USA.
Adler
H
H
Del-Pan
N C
NC
Kozlow
W
W
Sung
J
J
Fanslow
W
W
Rimm
I J
IJ
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D023201:CD40 Ligand; D005260:Female; D006561:Herpes Simplex / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D018259:Herpesvirus 1, Human; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000627:therapeutic use; D014184:Transplantation, Homologous
D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand