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J Infect Dis. 2011 Dec 1;204(11):1663-71. doi: 10.1093/infdis/jir624. Epub 2011 Oct 21.

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

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1
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.

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.

PMID:
22021622
PMCID:
PMC3203228
DOI:
10.1093/infdis/jir624
[Indexed for MEDLINE]
Free PMC Article
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