Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.

Journal Article (Journal Article)

RATIONALE: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects. OBJECTIVES: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV. METHODS: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort. MEASUREMENTS AND MAIN RESULTS: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]). The model included both protective (CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD4(+) T cells, CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD8(+) T cells) and detrimental (CD107a(+)/IFN-γ(+)/IL-2(-)/TNF-α(-) CD8(+) T cells) subsets. The model was robust in the validation cohort (concordance index 0.81 [SE, 0.103]). CONCLUSIONS: We identified and validated a specific T-cell polyfunctional response to CMV antigen stimulation that provides a clinically useful prediction of subsequent cytomegalovirus risk. This novel diagnostic approach could inform the optimal duration of individual prophylaxis.

Full Text

Duke Authors

Cited Authors

  • Snyder, LD; Chan, C; Kwon, D; Yi, JS; Martissa, JA; Copeland, CAF; Osborne, RJ; Sparks, SD; Palmer, SM; Weinhold, KJ

Published Date

  • January 1, 2016

Published In

Volume / Issue

  • 193 / 1

Start / End Page

  • 78 - 85

PubMed ID

  • 26372850

Pubmed Central ID

  • PMC4731614

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

Digital Object Identifier (DOI)

  • 10.1164/rccm.201504-0733OC


  • eng

Conference Location

  • United States