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Transpl Immunol. 2015 Jan;32(1):51-60. doi: 10.1016/j.trim.2014.10.005. Epub 2014 Nov 5.

Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.

Author information

1
Duke University Medical Center, Durham, NC, 27710, United States. Electronic address: kymberly.gowdy@nih.gov.
2
Duke University Medical Center, Durham, NC, 27710, United States.
3
Washington University School of Medicine, St. Louis, MO, 63110, United States.
4
Duke University Medical Center, Durham, NC, 27710, United States; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, United States.

Abstract

RATIONALE:

Bone marrow transplant (BMT) recipients experience frequent and severe respiratory viral infections (RVIs). However, the immunological mechanisms predisposing to RVIs are uncertain. Therefore, we hypothesized that antiviral T cell immunity is impaired as a consequence of allogeneic BMT, independent of pharmacologic immunosuppression, and is responsible for increased susceptibility to RVI.

METHODS:

Bone marrow and splenocytes from C57BL/6(H2(b)) mice were transplanted into B10.BR(H2(k)) (Allo) or C57BL/6(H2(b)) (Syn) recipients. Five weeks after transplantation, recipient mice were inoculated intranasally with mouse parainfluenza virus type 1 (mPIV-1), commonly known as Sendai virus (SeV), and monitored for relevant immunological and disease endpoints.

MAIN RESULTS:

Severe and persistent airway inflammation, epithelial injury, and enhanced mortality are found after viral infection in Allo mice but not in control Syn and non-transplanted mice. In addition, viral clearance is delayed in Allo mice as evidenced by prolonged detection of viral transcripts at Day 15 post-inoculation (p.i.) but not in control mice. In concert with these events, we also detected decreased levels of total and virus-specific CD8(+) T cells, as well as increased T cellexpression of inhibitory receptor programmed death-1 (PD-1), in the lungs of Allo mice at Day 8 p.i. Adoptive transfer of CD8(+) T cells from non-transplanted mice recovered from SeV infection into Allo mice at Day 8 p.i. restored normal levels of viral clearance, epithelial repair, and lung inflammation.

CONCLUSIONS:

Taken together these results indicate that allogeneic BMT results in more severe RVI based on the failure to develop an appropriate pulmonary CD8(+) T cell response, providing an important potential mechanism to target in improving outcomes of RVI after BMT.

KEYWORDS:

Bone marrow transplant; CD8(+) T cells; Lung; Respiratory virus

PMID:
25446809
PMCID:
PMC4277946
DOI:
10.1016/j.trim.2014.10.005
[Indexed for MEDLINE]
Free PMC Article

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