Treg and rapamycin effects on humoral immunity in young and old mice (84.12)

Abstract

Abstract Recently, the mTOR inhibitor rapamycin was shown to extend lifespan in mice even when administered at 20 months of age (Harrison et al. Nature 2009). Although studies have shown that it enhances vaccine efficacy and immune memory, others demonstrated an increase in Tregs and a depression of T cell proliferation. Thus, to assess the effect of rapamycin on humoral immunity, young and old mice were fed a rapamycin or control diet and then immunized 3 times with the protein antigen Omp34 from Aggregatibacter actinomycetemcomitans (Aa), a periodontal pathogen. As expected, rapamycin impaired antibody responses to Omp34 in young mice. In older mice, the humoral response was low and not enhanced by the drug. Serum cytokines were also measured and treatment with rapamycin had no effects. In order to address the role of Tregs, mice in each group were given 3 injections of αCD25 (functionally inactivates Tregs) or an isotype control antibody prior to each immunization. However, this treatment did not reverse the effects seen in antibody titers or cytokine levels, suggesting that Tregs alone do not account for the effects seen. After the last immunization, mice were challenged with viable Aa and protection was assessed. Rapamycin had no effect on protection, but surprisingly, antibody production to Aa in older mice was higher in those fed rapamycin. In younger mice, drug treatment had no effect. In conclusion, rapamycin’s effects on immunity should be assessed in old and young mice.