Chronic GvHD decreases antiviral immune responses in allogeneic BMT.
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 antiviral immunity and compared BM transplant recipients with cGvHD to control groups of allogeneic BM transplant recipients without GvHD. Mice with and without cGvHD received a nonlethal dose of murine cytomegalovirus (MCMV) +100 days after transplantation. Recipients with cGvHD had more weight loss and higher viral loads in the spleen and liver. MCMV infection led to greater than 25-fold expansion of donor spleen-derived MCMV peptide-specific tetramer-positive 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 immunosuppression 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 that cGvHD causes an intrinsic immunosuppression and explain, in part, the functional immunodeficiency in allogeneic transplant recipients.
Hossain
Mohammad S
MS
Department of Hematology and Oncology, Division of Stem Cell and Bone Marrow Transplantation, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
Roback
John D
JD
Pollack
Brian P
BP
Jaye
David L
DL
Langston
Amelia
A
Waller
Edmund K
EK
D000818:Animals; D001284:Atrophy / Q000276:immunology; D001782:Blood Donors; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007113:Immunity, Innate; D008221:Lymphoid Tissue / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018146:Muromegalovirus / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors