TY - JOUR
T1 - Primary cytomegalovirus phosphoprotein 65-specific CD8 + T-cell responses and T-bet levels predict immune control during early chronic infection in lung transplant recipients
AU - Pipeling, Matthew R.
AU - John, Emily R.
AU - Orens, Jonathan B.
AU - Lechtzin, Noah
AU - McDyer, John F.
N1 - Funding Information:
Acknowledgments. We thank the entire Johns Hopkins Lung Transplant clinical team, in particular the nurse coordinators, for their assistance with the care of the patients in this study. Financial support. This work was supported by National Institutes of Health (R01-AI079175 to J. F. M. and F32-HL091670 to M. R. P.). Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - 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.
AB - 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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U2 - 10.1093/infdis/jir624
DO - 10.1093/infdis/jir624
M3 - Article
C2 - 22021622
AN - SCOPUS:80155198513
VL - 204
SP - 1663
EP - 1671
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 11
ER -