Evaluation and significance of cytomegalovirus-specific cellular immune response in lung transplant recipients

Transplant Proc. 2011 May;43(4):1159-61. doi: 10.1016/j.transproceed.2011.03.024.


In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10(4) copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10(5) ± 2.4 × 10(5) copies/ml versus 7.9 × 10(3) ± 1.4 × 10(4) (P=.02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / virology
  • Chi-Square Distribution
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / prevention & control
  • Cytomegalovirus Infections / virology*
  • DNA, Viral / blood
  • DNA, Viral / isolation & purification
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunosuppressive Agents / therapeutic use
  • Italy
  • Lung Transplantation / immunology*
  • Male
  • Middle Aged
  • Monitoring, Immunologic / methods
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • DNA, Viral
  • Immunosuppressive Agents