title: 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.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.forename: Giampiero
authors.initials: G
authors.lastname: Piccinini
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Revello
authors.forename: Zhongde
authors.initials: Z
authors.lastname: Wang
authors.forename: Susan
authors.initials: S
authors.lastname: Markel
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000276:immunology* / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000276:immunology*; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology*; D011446:Prospective Studies; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000032:analysis / Q000276:immunology*; D014764:Viral Proteins / Q000032:analysis / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma