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Interleukin‐12 is sufficient to promote antigen‐independent interferon‐γ production by CD8 T cells in old mice
Author(s) -
Rottinghaus Erin K.,
Vesosky Bridget,
Turner Joanne
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03061.x
Subject(s) - cytotoxic t cell , il 2 receptor , interleukin 21 , biology , cd8 , cytokine , cd44 , t cell , interleukin 2 , immunology , interleukin 12 , interferon gamma , microbiology and biotechnology , antigen , immune system , cell , in vitro , biochemistry
Summary Numerous functional defects have been identified in naive T cells from aged mice, including deficiencies in proliferation, cytokine production and signal transduction. It is well documented that the ratio of naïve to memory T cells significantly decreases with age resulting in the majority of T cells from aged hosts expressing activated/memory T‐cell markers (CD44 hi ), yet it is unclear whether T cells with a CD44 hi phenotype in aged hosts are functionally equivalent to T cells with a similar phenotype in young hosts. We have identified a population of CD44 hi CD8 T cells in old mice that are capable of secreting interferon‐γ (IFN‐γ) in response to interleukin‐12 (IL‐12) stimulation. This occurred in the absence of T‐cell receptor engagement, a function that was not observed in CD8 T cells from young mice. This phenotype was associated with increased IL‐12 receptor β2 gene expression and IL‐12 induced signal transducer and activator of transcription 4 (STAT‐4) activation, even when CD8 T‐cell numbers from young and old mice were normalized for CD44 hi expression. Furthermore, we demonstrate that IL‐12‐induced STAT‐4 activation was required for T helper type 1 (Th1) cytokine‐induced IFN‐γ production in CD8 T cells. These data illustrate that old mice possess a specialized subset of CD44 hi CD8 T cells with an enhanced responsiveness to IL‐12, enabling these cells to produce substantial amounts of IFN‐γ in response to Th1 cytokine stimulation. We have therefore identified a functional difference in the populations of CD44 hi CD8 T cells from young and old mice, and believe that understanding age‐associated immunological changes is essential for helping the elderly combat deadly diseases.