Cargando…
Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses
BACKGROUND: Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell re...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1784110/ https://www.ncbi.nlm.nih.gov/pubmed/17156440 http://dx.doi.org/10.1186/1742-4933-3-11 |
_version_ | 1782132040152383488 |
---|---|
author | Komatsu, Haruki Inui, Ayano Sogo, Tsuyoshi Fujisawa, Tomoo Nagasaka, Hironori Nonoyama, Shigeaki Sierro, Sophie Northfield, John Lucas, Michaela Vargas, Anita Klenerman, Paul |
author_facet | Komatsu, Haruki Inui, Ayano Sogo, Tsuyoshi Fujisawa, Tomoo Nagasaka, Hironori Nonoyama, Shigeaki Sierro, Sophie Northfield, John Lucas, Michaela Vargas, Anita Klenerman, Paul |
author_sort | Komatsu, Haruki |
collection | PubMed |
description | BACKGROUND: Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. METHODS: One thousand and thirty-six people (Male/Female = 594/442, Age: 0–19 yr.; 959 subjects, 20–29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60–92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. RESULTS: We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. CONCLUSION: CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group. |
format | Text |
id | pubmed-1784110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-17841102007-01-31 Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses Komatsu, Haruki Inui, Ayano Sogo, Tsuyoshi Fujisawa, Tomoo Nagasaka, Hironori Nonoyama, Shigeaki Sierro, Sophie Northfield, John Lucas, Michaela Vargas, Anita Klenerman, Paul Immun Ageing Research BACKGROUND: Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. METHODS: One thousand and thirty-six people (Male/Female = 594/442, Age: 0–19 yr.; 959 subjects, 20–29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60–92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. RESULTS: We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. CONCLUSION: CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group. BioMed Central 2006-12-08 /pmc/articles/PMC1784110/ /pubmed/17156440 http://dx.doi.org/10.1186/1742-4933-3-11 Text en Copyright © 2006 Komatsu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Komatsu, Haruki Inui, Ayano Sogo, Tsuyoshi Fujisawa, Tomoo Nagasaka, Hironori Nonoyama, Shigeaki Sierro, Sophie Northfield, John Lucas, Michaela Vargas, Anita Klenerman, Paul Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title | Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title_full | Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title_fullStr | Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title_full_unstemmed | Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title_short | Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses |
title_sort | large scale analysis of pediatric antiviral cd8+ t cell populations reveals sustained, functional and mature responses |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1784110/ https://www.ncbi.nlm.nih.gov/pubmed/17156440 http://dx.doi.org/10.1186/1742-4933-3-11 |
work_keys_str_mv | AT komatsuharuki largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT inuiayano largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT sogotsuyoshi largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT fujisawatomoo largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT nagasakahironori largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT nonoyamashigeaki largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT sierrosophie largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT northfieldjohn largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT lucasmichaela largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT vargasanita largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses AT klenermanpaul largescaleanalysisofpediatricantiviralcd8tcellpopulationsrevealssustainedfunctionalandmatureresponses |