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Functional Exhaustion Limits CD4⁺ and CD8⁺ T-Cell Responses to Congenital Cytomegalovirus Infection

par Huygens, Ariane ;Appay, Victor;donner, catherine ;Marchant, Arnaud ;Lecomte, Sandra ;Tackoen, Marie ;Olislagers, Véronique ;Delmarcelle, Yves ;Burny, Wivine ;Van Rysselberge, Michel ;Liesnard, Corinne ;Larsen, Martin Røssel
Référence The Journal of infectious diseases, 212, 3, page (484-494)
Publication Publié, 2015-08

Article révisé par les pairs

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Résumé :

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.