Age-related changes in CD4 T cells of T cell receptor transgenic mice.

Much of the decrease in immunoresponsiveness seen in elderly populations is associated with changes in T cells responses. The observed functional changes include decreased responsiveness to T cell receptor stimulation and altered profiles of cytokine secretion. At the same time there is a decrease in the proportion of T cells that express a naive phenotype (CD44lo, CD45RBhi, CD62Lhi) and an increase in those that express a memory phenotype (CD44hi, CD45RBlo, CD62Llo). These changes are thought to result in the increased susceptibility to infection and decreased efficacy of vaccination that are observed in the elderly population. In this paper, we compare our published findings of the changes in antigen-specific T cell responsiveness using aged T cell receptor transgenic (TCR Tg) mice to what is known using conventional murine models. The specific antigen recognized by this transgenic T cell receptor apparently does not appear in the environment and the T cells expressing the Tg retain a naive phenotype. Similar to the findings in aged humans and rodents, the TCR Tg+ and TG- CD4 T cells from aged transgenic mice display decreased capacities for proliferation and cytokine secretion. Although the proportion of CD4 T cells that possess a memory phenotype increased in aged TCR Tg mice, they are Tg-. These findings support the presence of age-related deficiencies which do not depend on response to antigen. The implications of these findings are discussed.