Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses

Haruki Komatsu¹^,2 , Ayano Inui³ , Tsuyoshi Sogo³ , Tomoo Fujisawa³ , Hironori Nagasaka⁴ , Shigeaki Nonoyama¹ , Sophie Sierro⁵ , John Northfield⁵ , Michaela Lucas⁵ , Anita Vargas⁵ and Paul Klenerman⁵

¹Department of Pediatrics, National Defense Medical College, Saitama, Japan

²Department of Pediatrics, Toho University Sakura Hospital, Chiba, Japan

³Department of Pediatrics, Atami Hospital, International University Health and Welfare, Shizuoka, Japan

⁴Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

⁵Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK

author email corresponding author email

Immunity & Ageing 2006, 3:11doi:10.1186/1742-4933-3-11


Published:	8 December 2006

Abstract

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.