Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pediatrics; Department of Quantitative Health Sciences; Program in Molecular Medicine
Allergy and Immunology | Immunology and Infectious Disease | Pediatrics | Therapeutics | Translational Medical Research | Virus Diseases
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 (MIP1beta, CD107, IFNgamma, 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 MIP1beta- 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.
DOI of Published Version
J Clin Immunol. 2015 Apr;35(3):289-301. doi: 10.1007/s10875-015-0139-3. Epub 2015 Feb 25. Link to article on publisher's site.
Journal of clinical immunology
Gibson LL, Barysauskas C, McManus MM, Dooley S, Lilleri D, Fisher D, Srivastava T, Diamond DJ, Ruiz De Luzuriaga K. (2015). Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection. UMass Center for Clinical and Translational Science Supported Publications. https://doi.org/10.1007/s10875-015-0139-3. Retrieved from https://escholarship.umassmed.edu/umccts_pubs/46