CD8 T cells in old mice contribute to the innate immune response to Mycobacterium tuberculosis via IL-12p70 dependent and antigen independent production of IFN-gamma - Related Articles
CD8 T cells in old mice contribute to the innate immune response to Mycobacterium tuberculosis via IL-12p70 dependent and antigen independent production of IFN-gamma
Infect Immun. 2009 May 26;
Authors: Vesosky B, Rottinghaus EK, Davis C, Turner J
Elderly individuals have increased morbidity and mortality associated with infectious diseases, due in part to the progressive age associated decline in immune function. Despite this, the old mouse model of Mtb infection has revealed a CD8 and IFN-gamma dependent early resistance to infection. In this study we investigated the mechanism by which CD8 T cells from old mice contributed to the early immune response to Mtb. Following a low dose aerosol infection with Mtb, CD8 T cells were identified as a dominant source of IFN-gamma expression in the lungs of old mice early after infection, before the typical onset of antigen specific immunity. In addition, Mtb induced IFN-gamma production by CD8 T cells isolated from naïve old mice was MHC Class I independent but dependent on IL-12p70, confirming an innate role of CD8 T cells during Mtb infection. Moreover, the ability of CD8 T cells from old mice to produce increased innate IFN-gamma in response to Mtb infection was defined as a unique function of CD8 T cells from old mice and not the aged lung environment. Finally, we have identified increased expression of SET as one possible mechanism by which CD8 T cells from old mice produce enhanced IFN-gamma. Additional characterization of the signaling events that lead to enhanced innate IFN-gamma production by CD8 T cells in old mice may lead to novel strategies to further enhance or perpetuate beneficial immune responses in the elderly.
PMID: 19470747 [PubMed - as supplied by publisher] [Tuberculosis Pulmonary]