title: Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection.
abstract: OBJECTIVE
  CMV infection remains a priority for vaccine development. Vaccination of infants could modify congenital infection and provide lifetime immunity. Properties of CMV-specific T cells associated with control of viral replication in early life have not been fully defined.
  
  
  METHODS
  CMV-specific CD4 and CD8 T cell responses were investigated in infants with congenital CMV infection and compared to adults with primary or chronic infection. PBMC were stimulated with UL83 (pp65) or UL122 (IE-2) peptide pools then stained with antibodies to markers of T cell subset (CD4 or CD8), phenotype (CD45RA, CCR7), or function (MIP1β, CD107, IFNγ, IL2) for flow cytometry analysis.
  
  
  RESULTS
  Detection of CMV pp65-specific CD4 T cells was less common in infants than adults. Responder cells were primarily effector memory (EM, CD45RA-CCR7-) in adults, but mixed memory subsets in infants. Detection of CMV pp65-specific CD8 T cells did not differ between the groups, but infants had lower frequencies of total responding cells and of MIP1β- or CD107-expressing cells. Responder cells were EM or effector memory RA (CD45RA + CCR7-) in all groups. Polyfunctional T cells were less commonly detected in infants than adults. Responses to IE-2 were detected in adults but not infants. All infants had detectable circulating CMV DNA at initial study (versus 60 % of adults with primary infection) despite longer duration of CMV infection.
  
  
  CONCLUSIONS
  Reduced frequencies and altered functional profile of CMV-specific CD4 and CD8 T cell responses were detected in infants compared to adults, and were associated with persistent CMV DNA in peripheral blood.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA, laura.gibson@umassmed.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.forename: Constance M
authors.initials: CM
authors.lastname: Barysauskas
authors.forename: Margaret
authors.initials: M
authors.lastname: McManus
authors.forename: Sheryl
authors.initials: S
authors.lastname: Dooley
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
authors.forename: Donna
authors.initials: D
authors.lastname: Fisher
authors.forename: Tumul
authors.initials: T
authors.lastname: Srivastava
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000151:congenital* / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn
chemical_list: D004279:DNA, Viral