Abstract

Abstract One risk factor for reactivation of latent M. tuberculosis (MTB) is old age. Although there are significant data in elderly and nursing home patients on clinical matters such as use of two-step PPD testing, there are a severe paucity of data on changes in MTB-specific immune responses that occur with aging. We have studied MTB-specific immune responses using 13-color intracytoplasmic flow cytometry analysis of CD4+ and CD8+ memory T cell subsets simultaneously examining their expression of IFN-gamma, IL-2, MIP1-alpha, and perforin after stimulation with the MTB-antigen PPD. Data from 13 latently MTB-infected PPD+ older subjects (mean age 77 range 61-89) showed that MTB-specific responses from CD4+ and CD8+ T cells were maintained compared to 8 younger PPD+ subjects (mean age 31 range 23-40). Surprisingly, frequencies of MTB-specific IL-2 secreting effector and central memory CD4+ T cell were higher in older subjects (mean 1.1%) than in younger persons (mean 0.22%, p<0.05). In older subjects, many of these MTB-specific CD4+ T cells only secreted IL-2 after stimulation while there was no defect in their ability to produce the full range of cytokines studied when stimulated with mitogen. Overall, as there was no defect in MTB-specific T cells in older persons, these data support a need to further broaden the T cell studies as well to expand to other areas such as potential deficits in macrophage function.

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