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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Allografts
  • Animals
  • Bone Marrow Transplantation*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / transplantation
  • Immunity, Cellular*
  • Male
  • Mice
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / therapy
  • Respirovirus Infections / etiology
  • Respirovirus Infections / immunology*
  • Respirovirus Infections / pathology
  • Respirovirus Infections / therapy
  • Sendai virus / immunology*