Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects
| Autor: | Christian Pelte, Paul R. Sleath, Bridget L. Mitchell, John B. Edgar, Florian Kern, Andrew W. Sylwester, Jay A. Nelson, Cara Taormina, Kenneth H. Grabstein, Nancy Ann Hosken, Franziska Ruchti, Louis J. Picker |
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| Rok vydání: | 2005 |
| Předmět: |
Human cytomegalovirus
Adult CD4-Positive T-Lymphocytes Male T cell viruses Immunology Cytomegalovirus Immunodominance Biology CD8-Positive T-Lymphocytes Virus Article 03 medical and health sciences Open Reading Frames 0302 clinical medicine Immune system medicine Immunogenetics Immunology and Allergy Cytotoxic T cell Humans Serologic Tests 030304 developmental biology 0303 health sciences Middle Aged medicine.disease Flow Cytometry Virology 3. Good health medicine.anatomical_structure Viral replication Cytomegalovirus Infections Female Peptides Immunologic Memory CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4(+) and/or CD8(+) T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average approximately 10% of both the CD4(+) and CD8(+) memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8(+) T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans. |
| Databáze: | OpenAIRE |
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