Th1 Cytokines Facilitate CD8-T-Cell-Mediated Early Resistance to Infection withMycobacterium tuberculosisin Old Mice

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Abstract
Numerous immunological defects begin to emerge as an individual ages, the consequence of which is heightened susceptibility to infectious diseases. Despite this decline in immune function, old mice display an early transient resistance toMycobacterium tuberculosisinfection in the lung, which is dependent on CD8 T cells and gamma interferon (IFN-γ) production. In this study, we investigated the mechanism of resistance by examining the CD8-T-cell phenotype and function in old naïve andM. tuberculosis-infected mice. Pulmonary CD8 T cells from naïve old mice expressed cell surface markers of memory in addition to receptors for several Th1 cytokines. Stimulation of lung cells from naïve old mice with a combination of Th1 cytokines (interleukin-2 [IL-2], IL-12, and IL-18) resulted in nonspecific production of IFN-γ by memory CD8 T cells. Following aerosol infection withM. tuberculosis, the lungs of old mice contained significantly more IL-12, IL-18, and IFN-γ than the lungs of young mice contained. Together, these data demonstrate that the increased and early production of Th1 cytokines in the lungs ofM. tuberculosis-infected old mice, in combination with CD8 T cells that can nonspecifically produce IFN-γ, leads to transient control ofM. tuberculosisgrowth in the lungs of old mice. Further characterization of this mechanism should provide essential information regarding the aging immune system and should contribute to the development of novel strategies to decrease the morbidity and mortality of the aging population associated with infectious diseases.