title: Functional Exhaustion Limits CD4+ and CD8+ T-Cell Responses to Congenital Cytomegalovirus Infection.
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.
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi.
authors: Ariane
authors: A
authors: Huygens
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi.
authors: Sandra
authors: S
authors: Lecomte
authors: Department of Neonatology.
authors: Marie
authors: M
authors: Tackoen
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi.
authors: Véronique
authors: V
authors: Olislagers
authors: ImmuneHealth, Gosselies, Belgium.
authors: Yves
authors: Y
authors: Delmarcelle
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi.
authors: Wivine
authors: W
authors: Burny
authors: Department of Obstetrics and Gynecology, Hôpital Saint-Pierre.
authors: Michel
authors: M
authors: Van Rysselberge
authors: Department of Virology.
authors: Corinne
authors: C
authors: Liesnard
authors: Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, France.
authors: Martin
authors: M
authors: Larsen
authors: Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, France.
authors: Victor
authors: V
authors: Appay
authors: Department of Obstetrics and Gynecology, Hôpital Erasme, Brussels.
authors: Catherine
authors: C
authors: Donner
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi ImmuneHealth, Gosselies, Belgium.
authors: Arnaud
authors: A
authors: Marchant
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines
keywords: CD4 T cell; CD8 T cell; congenital infection; cytomegalovirus; exhaustion; fetus