Reduced Frequencies of Polyfunctional CMV-Specific T Cell Responses in Infants with Congenital CMV Infection

Laura Gibson, Constance M. Barysauskas, Margaret McManus, Sheryl Dooley, Daniele Lilleri, Donna Fisher, Tumul Srivastava, Don J. Diamond, Katherine Luzuriaga

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)289-301
Number of pages13
JournalJournal of Clinical Immunology
Volume35
Issue number3
DOIs
Publication statusPublished - 2015

Keywords

  • congenital
  • Cytomegalovirus
  • host immunity
  • neonate
  • polyfunction
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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