LAUSR

Abstract Senior individuals older than 65 years of age are at a disproportionally higher risk of developing pneumonia. Impaired capacity to defend against airway infections may be one of the reasons. It is generally believed that weaker regulatory T cell responses may be beneficial to host defense against pathogens. In senior patients with community‐acquired bacterial pneumonia, we investigated the frequencies and functions of regulatory T cells. Interestingly, we found that compared to age‐ and sex‐matched healthy controls, senior pneumonia patients presented lower frequencies of Foxp3‐expressing and Helios‐expressing CD4+ T cells. The quantity of Foxp3 and Helios being expressed, measured by their mRNA transcription levels, was also lower in CD4+ T cells from pneumonia patients. Furthermore, following TCR and TGF‐&bgr; stimulation, pneumonia patients presented impaired capacity to upregulate Foxp3 and Helios. Functional analyses revealed that CD4+ T cells from pneumonia patients secreted lower amounts of IL‐10 and TGF‐&bgr;, two cytokines critical to regulatory T cell‐mediated suppression. Also, the expression of granzyme B and perforin, which were cytolytic molecules potentially utilized by regulatory T cells to mediate the elimination of antigen‐presenting cells and effector T cells, were reduced in CD4+CD25+ T cells from senior pneumonia patients. In addition, the CD4+CD25+ T cells from senior pneumonia patients presented reduced capacity to suppress effector CD4+ and CD8+ T cell proliferation. Moreover, the value of pneumonia severity index was inversely correlated with several parameters of regulatory T cell function. Together, our results demonstrated that senior pneumonia patients presented a counterintuitive impairment in regulatory T cell responses that was associated with worse prognosis.