Research

Effect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors

María Luisa Pita-Lopez^1,4 , Inmaculada Gayoso¹ , Olga DelaRosa¹ , Javier G Casado² , Corona Alonso¹ , Elisa Muñoz-Gomariz³ , Raquel Tarazona² and Rafael Solana¹

¹  University of Cordoba, Department of Cellular Biology, Physiology and Immunology, Faculty of Medicine, Cordoba, Spain

²  University of Extremadura, Department of Physiology, Immunology Unit, Caceres, Spain

³  Research Methodology Unit, H. U. Reina Sofia, Cordoba, Spain

⁴  Molecular Biology and Immunology Unit, Department of Health and Well-being, South University Center, University of Guadalajara, Guzman City, Jalisco, Mexico

author email corresponding author email

Immunity & Ageing 2009, 6:11doi:10.1186/1742-4933-6-11

Published:	28 August 2009

Abstract

Background

Ageing is associated with changes in the immune system with substantial alterations in T-lymphocyte subsets. Cytomegalovirus (CMV) is one of the factors that affect functionality of T cells and the differentiation and large expansions of CMV pp65-specific T cells have been associated with impaired responses to other immune challenges. Moreover, the presence of clonal expansions of CMV-specific T cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious diseases in the elderly. In this study, we analyse the effect of ageing on the phenotype and frequency of CMV pp65-specific CD8 T cell subsets according to the expression of CCR7, CD45RA, CD27, CD28, CD244 and CD85j.

Results

Peripheral blood from HLA-A2 healthy young, middle-aged and elderly donors was analysed by multiparametric flow cytometry using the HLA-A*0201/CMV pp65_495–504 (NLVPMVATV) pentamer and mAbs specific for the molecules analysed. The frequency of CMV pp65-specific CD8 T cells was increased in the elderly compared with young and middle-aged donors. The proportion of naïve cells was reduced in the elderly, whereas an age-associated increase of the CCR7^null effector-memory subset, in particular those with a CD45RA^dim phenotype, was observed, both in the pentamer-positive and pentamer-negative CD8 T cells. The results also showed that most CMV pp65-specific CD8 T cells in elderly individuals were CD27/CD28 negative and expressed CD85j and CD244.

Conclusion

The finding that the phenotype of CMV pp65-specific CD8 T cells in elderly individuals is similar to the predominant phenotype of CD8 T cells as a whole, suggests that CMV persistent infections contributes to the age-related changes observed in the CD8 T cell compartment, and that chronic stimulation by other persistent antigens also play a role in T cell immunosenescence. Differences in subset distribution in elderly individuals showing a decrease in naive and an increase in effector-memory CD8 T cells may be relevant in the age-associated defective immune response.