Impairment of maintenance and function of influenza‐specific T cell memory in diet‐induced obese mice

Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet‐induced obese mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine if the problem resided in a failure to generate and/or maintain memory T cells and/or a failure in T cell memory function, obese and lean mice were infected with influenza X‐31. At day 31 post infection, obese memory T cells had a >50% decrease in response to stimulation by influenza PR8‐pulsed dendritic cells from lean mice. This defect was specific to memory T cells, as dendritic cells from obese mice present antigen normally to memory T cells from lean mice. At 80 days post infection, obese mice had a 10% reduction in memory T cell numbers. This reduction may be due to significantly reduced memory T cell expression of IL‐2Rβ (CD122), but not IL‐7Rα (CD127), which are both required for memory cell maintenance. Since leptin has been associated with both IL‐15 and CD122, peripheral leptin resistance in the obese mice may be a contributing factor to the impairment. It is imperative to understand how the obese state alters ability of memory T cells to function and be maintained. Moreover, impairment in maintenance of functional memory responses has significant implications for vaccine efficacy in an obese population. Grant Funding Source: DK56350