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
Authors
Gibson, Laura LPiccinini, Giampiero
Lilleri, Daniele
Revello, Maria Grazia
Wang, Zhongde
Markel, Susan F.
Diamond, Don J.
Luzuriaga, Katherine
Document Type
Journal ArticlePublication Date
2004-02-07Keywords
CD8-Positive T-LymphocytesCell Line, Transformed
Child, Preschool
Cytomegalovirus
Cytomegalovirus Infections
Cytotoxicity Tests, Immunologic
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte
Female
HLA-A2 Antigen
Humans
Immediate-Early Proteins
Immunophenotyping
Infant
Infant, Newborn
Interferon Type II
Phosphoproteins
Prospective Studies
Viral Load
Viral Matrix Proteins
Viral Proteins
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2004 Feb 15;172(4):2256-64.
DOI
10.4049/jimmunol.172.4.2256Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38231PubMed ID
14764694Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.172.4.2256
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