Immunosenescence: potential causes and strategies for reversal

Age-related deterioration in immune function has been recognized in many sp ecies. In humans the clinical manifestation of such immune dysfunction is a ge-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory inves tigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function an d irt replicative ability following stimulus with antigen, mitogens or anti -CDS antibody. These changes in the properties of peripheral T cells are th ought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymi c microenvironment linked to a reduction in the level of available interleu kin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy w ith increased thymopoiesis. This provides the potential to reverse the immu ne dysfunction seen in the peripheral T cell pool by replacing old cells wi th new output generated in the thymus. Problems to overcome in order for su ch an experimental therapy to be successful require careful analysis in ord er to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the pe ripheral T cell pool.