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.
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Citation: 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.
Gibson, Laura L.; Barysauskas, Constance; McManus, Margaret M.; Dooley, Sheryl; Lilleri, Daniele; Fisher, Donna; Srivastava, Tumul; Diamond, Don J.; and Ruiz De Luzuriaga, Katherine, "Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection" (2015). UMass Center for Clinical and Translational Science Supported Publications. 46.