Human cytomegalovirus proteins pp65 and immediate early protein 1 are common targets for CD8+ T cell responses in children with congenital or postnatal human cytomegalovirus infection

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dc.contributor.authorGibson, Laura L
dc.contributor.authorPiccinini, Giampiero
dc.contributor.authorLilleri, Daniele
dc.contributor.authorRevello, Maria Grazia
dc.contributor.authorWang, Zhongde
dc.contributor.authorMarkel, Susan F.
dc.contributor.authorDiamond, Don J.
dc.contributor.authorLuzuriaga, Katherine
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Pediatrics
dc.date2022-08-11T08:09:31.000
dc.date.accessioned2022-08-23T16:33:59Z
dc.date.available2022-08-23T16:33:59Z
dc.date.issued2004-02-07
dc.date.submitted2009-03-10
dc.description.abstractRecombinant modified vaccinia Ankara- and peptide-based IFN-gamma ELISPOT assays were used to detect and measure human CMV (HCMV)-specific CD8(+) T cell responses to the pp65 (UL83) and immediate early protein 1 (IE1; UL123) gene products in 16 HCMV-infected infants and children. Age at study ranged from birth to 2 years. HCMV-specific CD8(+) T cells were detected in 14 (88%) of 16 children at frequencies ranging from 60 to >2000 spots/million PBMC. Responses were detected as early as 1 day of age in infants with documented congenital infection. Nine children responded to both pp65 and IE1, whereas responses to pp65 or IE1 alone were detected in three and two children, respectively. Regardless of the specificity of initial responses, IE1-specific responses predominated by 1 year of age. Changes in HCMV epitopes targeted by the CD8(+) T cell responses were observed over time; epitopes commonly recognized by HLA-A2(+) adults with latent HCMV infection did not fully account for responses detected in early childhood. Finally, the detection of HCMV-specific CD8(+) T cell responses was temporally associated with a decrease in peripheral blood HCMV load. Taken altogether, these data demonstrate that the fetus and young infant can generate virus-specific CD8(+) T cell responses. Changes observed in the protein and epitope-specificity of HCMV-specific CD8(+) T cells over time are consistent with those observed after other primary viral infections. The temporal association between the detection of HCMV-specific CD8(+) T cell responses and the reduction in blood HCMV load supports the importance of CD8(+) T cells in controlling primary HCMV viremia.
dc.identifier.citation<p>J Immunol. 2004 Feb 15;172(4):2256-64.</p>
dc.identifier.contextkey770085
dc.identifier.doi10.4049/jimmunol.172.4.2256
dc.identifier.issn0022-1767 (Print)
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1107
dc.identifier.pmid14764694
dc.identifier.submissionpathoapubs/1107
dc.identifier.urihttps://hdl.handle.net/20.500.14038/38231
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=14764694&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.172.4.2256
dc.source.issue4
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.pages2256-64
dc.source.volume172
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCell Line, Transformed
dc.subjectChild, Preschool
dc.subjectCytomegalovirus
dc.subjectCytomegalovirus Infections
dc.subjectCytotoxicity Tests, Immunologic
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectEpitopes, T-Lymphocyte
dc.subjectFemale
dc.subjectHLA-A2 Antigen
dc.subjectHumans
dc.subjectImmediate-Early Proteins
dc.subjectImmunophenotyping
dc.subjectInfant
dc.subjectInfant, Newborn
dc.subjectInterferon Type II
dc.subjectPhosphoproteins
dc.subjectProspective Studies
dc.subjectViral Load
dc.subjectViral Matrix Proteins
dc.subjectViral Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleHuman cytomegalovirus proteins pp65 and immediate early protein 1 are common targets for CD8+ T cell responses in children with congenital or postnatal human cytomegalovirus infection
dc.typeJournal Article
dspace.entity.typePublication
html.description.abstract<p>Recombinant modified vaccinia Ankara- and peptide-based IFN-gamma ELISPOT assays were used to detect and measure human CMV (HCMV)-specific CD8(+) T cell responses to the pp65 (UL83) and immediate early protein 1 (IE1; UL123) gene products in 16 HCMV-infected infants and children. Age at study ranged from birth to 2 years. HCMV-specific CD8(+) T cells were detected in 14 (88%) of 16 children at frequencies ranging from 60 to >2000 spots/million PBMC. Responses were detected as early as 1 day of age in infants with documented congenital infection. Nine children responded to both pp65 and IE1, whereas responses to pp65 or IE1 alone were detected in three and two children, respectively. Regardless of the specificity of initial responses, IE1-specific responses predominated by 1 year of age. Changes in HCMV epitopes targeted by the CD8(+) T cell responses were observed over time; epitopes commonly recognized by HLA-A2(+) adults with latent HCMV infection did not fully account for responses detected in early childhood. Finally, the detection of HCMV-specific CD8(+) T cell responses was temporally associated with a decrease in peripheral blood HCMV load. Taken altogether, these data demonstrate that the fetus and young infant can generate virus-specific CD8(+) T cell responses. Changes observed in the protein and epitope-specificity of HCMV-specific CD8(+) T cells over time are consistent with those observed after other primary viral infections. The temporal association between the detection of HCMV-specific CD8(+) T cell responses and the reduction in blood HCMV load supports the importance of CD8(+) T cells in controlling primary HCMV viremia.</p>
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