Journal of Clinical Immunology

, Volume 35, Issue 3, pp 289–301 | Cite as

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
Original Research

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.

Keywords

Cytomegalovirus congenital neonate host immunity T cells polyfunction 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Laura Gibson
    • 1
    • 2
    • 10
  • Constance M. Barysauskas
    • 4
    • 5
  • Margaret McManus
    • 2
  • Sheryl Dooley
    • 2
    • 3
  • Daniele Lilleri
    • 7
  • Donna Fisher
    • 8
  • Tumul Srivastava
    • 9
  • Don J. Diamond
    • 9
  • Katherine Luzuriaga
    • 2
    • 6
  1. 1.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Boston Heart DiagnosticsFraminghamUSA
  4. 4.Department of Quantitative Health SciencesUniversity of Massachusetts Medical SchoolWorcesterUSA
  5. 5.Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  6. 6.Program in Molecular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  7. 7.Laboratori Sperimentali di Ricerca-Area TrapiantologicaFondazione IRCCS Policlinico San MatteoPaviaItaly
  8. 8.Department of Pediatrics, Baystate Children’s HospitalTufts University School of MedicineSpringfieldUSA
  9. 9.Division of Translational Vaccine ResearchBeckman Research Institute of the City of HopeDuarteUSA
  10. 10.Infectious Diseases and ImmunologyUMassMemorial Medical CenterWorcesterUSA

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