Acute graft-versus-host disease impairs anti-viral immunity and leads to fulminant CMV disease (TRAN1P.937)
Autor: | Mariapia Degli-Esposti, Matthew Wikstrom, Rachel Kuns, Peter Fleming, Siok-Keen Tey, Christopher Andoniou, Geoffrey Hill |
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Rok vydání: | 2015 |
Předmět: | |
Zdroj: | The Journal of Immunology. 194:140.19-140.19 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.194.supp.140.19 |
Popis: | Viral infection is a common, life-threatening complication of allogeneic bone marrow transplantation (BMT), particularly in the presence of graft-versus-host disease (GVHD). The inability to mount protective anti-viral immunity is well recognized, yet the defects remain unclear. Using cytomegalovirus (CMV) as the prototype pathogen, we delineated the cause of the disease that arises following infection, as well as the mechanisms that lead to the inability to mount effective anti-viral immunity in this setting. While infection was self-limiting after syngeneic BMT, CMV infected mice with GVHD developed a fulminant necrotizing hepatitis directly associated with extensive CMV cytopathy. GVHD induced profound defects in dendritic cells (numerical and resistance to infection) that profoundly impaired viral antigen presentation, preventing the priming of CMV-specific CD8+ T cells. Changes indicative of T cell exhaustion were also observed. The transfer of virus-specific CD8+ T cells pre-infection circumvented the priming defect and provided protective immunity. Notably, efficacious anti-viral immunity could still be generated when T cells were transferred at the time of BMT, a month prior to infection, despite concurrent GVHD. These data demonstrate the importance of avoiding GVHD when reconstructing anti-viral immunity after BMT, and highlight the mechanisms by which the adoptive transfer of virus-specific T cells overcome the endogenous defects in priming invoked by GVHD. |
Databáze: | OpenAIRE |
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