Primary cytomegalovirus phosphoprotein 65-specific CD8 + T-cell responses and T-bet levels predict immune control during early chronic infection in lung transplant recipients

Matthew R. Pipeling, Emily R. John, Jonathan B. Orens, Noah Lechtzin, John F. McDyer

Research output: Contribution to journalArticle

Abstract

Background.Cytomegalovirus (CMV) remains an important pathogen in solid organ transplantation, particularly lung transplantation. Lung transplant recipients (LTRs) mismatched for CMV (donor positive/recipient negative [D +R -]) are at highest risk for active CMV infection and have increased mortality. However, the correlates of immune control during chronic CMV infection remain incompletely understood.Methods.We prospectively studied 22 D +R - LTRs during primary CMV infection and into chronic infection. Immune responses during primary infection were analyzed for association with viral relapse during early chronic infection.Results.Primary CMV infection was characterized by a striking induction of T-box transcription factor (T-bet) in CD8 + T cells. CMV-specific effector CD8 + T cells were found to be T-bet +. After primary infection, 7 LTRs lacked immune control with relapsing viremia during early chronic infection. LTRs with relapsing viremia had poor induction of T-bet and low frequencies of phosphoprotein 65 (pp65)-specific CD8 + effector T cells during primary infection. However, frequencies of IE1-specific CD8 + effector T cells during primary infection were not associated with early relapsing viremia.Conclusions.T-bet plays an important role in coordinating CD8 + effector responses to CMV during primary infection. Moreover, CD8 + T-bet induction and pp65-specific CD8 + effector responses at the time of primary infection are important predictors of immune control of CMV during early chronic infection.

Original languageEnglish (US)
Pages (from-to)1663-1671
Number of pages9
JournalJournal of Infectious Diseases
Volume204
Issue number11
DOIs
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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