1. Functional Exhaustion Limits CD4+ and CD8+ T-Cell Responses to Congenital Cytomegalovirus Infection.
- Author
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Huygens, Ariane, Lecomte, Sandra, Tackoen, Marie, Olislagers, Véronique, Delmarcelle, Yves, Burny, Wivine, Van Rysselberge, Michel, Liesnard, Corinne, Larsen, Martin, Appay, Victor, Donner, Catherine, and Marchant, Arnaud
- Subjects
HUMAN cytomegalovirus diseases ,IMMUNE response ,T cells ,CD4 antigen ,CD8 antigen ,CYTOKINES ,PROGRAMMED cell death 1 receptors - Abstract
Background. Cytomegalovirus (CMV) infection during fetal life causes severe symptoms and is associated with prolonged viral excretion. Previous studies reported low CD4
+ T-cell responses to CMV infection in early life, contrasting with large responses of effector CD8+ T cells. The mechanisms underlying the defective CD4+ T-cell responses and the possible dissociation with CD8+ T-cell responses have not been clarified. Methods. The magnitude and the quality of the fetal CD8+ and CD4+ T-cell responses to CMV infection were compared to those of adults with primary or chronic infection. Results. In utero CMV infection induced oligoclonal expansions of fetal CD4+ and CD8+ T lymphocytes expressing a T-helper type 1 or Tc1 effector phenotype similar to that of adult CMV-specific cells. However, the effector cytokine responses and the polyfunctionality of newborn CD4+ and CD8+ T cells were markedly lower than those of adult cells. This reduced functionality was associated with a higher expression of the programmed death 1 inhibitory receptor, and blockade of this receptor increased newborn T-cell responses. Conclusions. Functional exhaustion limits effector CD4+ and CD8+ T-lymphocyte responses to CMV during fetal life. [ABSTRACT FROM AUTHOR]- Published
- 2015
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