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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature
Haruki Komatsu1, Ayano Inui, Tsuyoshi Sogo
1Department of Pediatrics, National Defense Medical College, Saitama, Japan. haruki-komatsu@chive.ocn.ne.jp
Insights
Cytomegalovirus (CMV) infection triggers robust CD8+ T cell responses in children, maintaining high frequencies throughout life. Unlike adults, children do not show T cell "inflation," suggesting potential for early vaccine strategies.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Cellular immunity is vital for controlling cytomegalovirus (CMV) infection.
- Substantial CMV-specific T cells accumulate over a lifetime.
- Pediatric T cell responses to CMV are not well understood.
Purpose of the Study:
- To characterize the quantity and quality of T cell responses in pediatric populations against CMV.
- To compare CMV-specific CD8+ T cell responses in children versus adults.
Main Methods:
- Analyzed HLA typing and HLA-A2 antigen in 1036 individuals (ages 0-19 years) and 50 elderly individuals.
- Measured frequencies, phenotype, and function of CD8+ T cells targeting two immunodominant CMV pp65 epitopes.
- Compared T cell responses between pediatric and adult cohorts.
Main Results:
- Consistently high frequencies of phenotypically mature CMV-specific CD8+ T cells were observed in children, including infants.
- These CD8+ T cells maintained functionality across all age groups studied.
- Evidence of memory T cell "inflation" was only observed in older adults, not children.
Conclusions:
- CMV elicits strong CD8+ T cell responses in infants, with large pools maintained throughout childhood.
- CMV shapes the CD8+ T cell compartment, but population-level increases are not seen in childhood/adulthood, contrasting with older adults.
- Large-scale analysis of peptide-specific T cell responses in infants is feasible, supporting vaccine strategies for major pathogens in this age group.
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.
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