The effect of age on the phenotype and function of developing thymocytes.
The immune system declines with age leading to a progressive deterioration in the ability to respond to infection and vaccination. Age-associated thymic involution is one of the most recognized changes in the ageing immune system and is believed to be a major contributor towards immunosenescence; however, the precise mechanisms involved in age-associated thymic involution remain unclear. In order to gain further insight into the effect of ageing on T-cell development, steady-state thymopoiesis was studied in mice ranging from 1 to 18 months of age. There was a decrease in thymic cellularity with age, but the most dramatic loss occurred early in life. Although there were no alterations in the proportion of the major thymocyte subsets, there was a significant decline in the expression of other key molecules including CD3 and CD24. There was a decline in the ability of thymocytes from older mice to respond to mitogens, which was demonstrated by a failure to up-regulate expression of the activation marker CD69 and to enter the G(2)--M phase of the cell cycle. This was concurrent with an increased resistance to apoptosis in thymocytes from aged animals. Together, these results suggest that T cells may be flawed even before exiting to the periphery and that this could contribute to the age-associated decline in immune function.
Aw
D
D
Infection & Immunity and Genes & Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Silva
A B
AB
Palmer
D B
DB
D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002452:Cell Count; D002453:Cell Cycle / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D051379:Mice; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D015703:Antigens, CD