Submitted April 20, 2006
Accepted January 16, 2007
Chronic GvHD decreases anti-viral immune responses in allogeneic BMT
Mohammad S Hossain, John D Roback, Brian P Pollack, David L. Jaye, Amelia Langston, and Edmund K Waller*
Department of Hematology and Oncology, Division of Stem Cell and Bone Marrow Transplantation, Winship Cancer Institute, Emory University, Atlanta, GA, United States
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
Departments of Dermatology and Pathology, Emory University, Atlanta, GA, United States
* Corresponding author; email: ewaller{at}emory.edu.
Chronic graft-versus-host-disease (cGvHD) is associated with functional immunodeficiency and an increased risk of opportunistic infections in allogeneic bone marrow transplantation (BMT). We used a parent to F1 model of allogeneic BMT to test the hypothesis that cGvHD leads to impaired antigen-specific anti-viral immunity and compared BMT recipients with cGvHD to control groups of allogeneic BMT recipients without GvHD. Mice with and without cGvHD received a non-lethal dose of murine cytomegalovirus (MCMV) +100 days post transplant. Recipients with cGvHD had more weight loss and higher viral loads in the spleen and liver. MCMV infection led to >25-fold expansion of donor-spleen-derived MCMV-peptide-specific-tetramer+ CD8+ T-cells in blood of transplant recipients with and without cGvHD, but mice with cGvHD had far fewer antigen-specific T-cells in peripheral tissues and secondary lymphoid organs. The immuno-suppression associated with cGvHD was confirmed by vaccinating transplant recipients with and without cGvHD using a recombinant Listeria expressing MCMV early protein (Lm-MCMV). Secondary adoptive transfer of lymphocytes from donor mice with or without cGvHD into lymphopenic congenic recipients showed that cGvHD impaired tissue-specific homing of antigen specific T-cells. These results indicate cGvHD causes an intrinsic immuno-suppression and explain, in part, the functional immunodeficiency in allogeneic transplant recipients.
