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  • Title: Primary cytomegalovirus phosphoprotein 65-specific CD8+ T-cell responses and T-bet levels predict immune control during early chronic infection in lung transplant recipients.
    Author: Pipeling MR, John ER, Orens JB, Lechtzin N, McDyer JF.
    Journal: J Infect Dis; 2011 Dec 01; 204(11):1663-71. PubMed ID: 22021622.
    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.
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