期刊
BLOOD
卷 109, 期 10, 页码 4548-4556出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-04-017442
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- NCI NIH HHS [CA-74364, R01 CA074364] Funding Source: Medline
- NHLBI NIH HHS [R01 HL070997, HL70997] Funding Source: Medline
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.
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