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Production1

* Trudeau Institute, Saranac Lake, NY 12983; and
Upstate Biotechnology, Lake Placid, NY 12946
The expression of IFN-
is a hallmark of Th1 cells and CD8+ effector T cells and is the signature cytokine of type 1 responses. However, it is not known whether T cells are homogeneous in their capacity to produce IFN-
, whether this potential varies between tissues, and how it relates to the production of other effector molecules. In the present study we used bicistronic IFN-
-enhanced yellow fluorescent protein (IFN-
-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-
expression at the single cell level. The eYFP fluorescence of Th1 cells and CD8+ effector T cells was broadly heterogeneous even before cell division and correlated with both the abundance of IFN-
transcripts and the secretion of IFN-
upon stimulation. CD4+ and CD8+ T cells of influenza-infected mice revealed a similarly heterogeneous IFN-
expression, and eYFPhigh cells were only found in the infected lung. Ag-specific T cells were in all examined tissues eYFP+, but also heterogeneous in their reporter fluorescence, and eYFPhigh cells were also restricted to the infected lung. A similar heterogeneity was observed in Toxoplasma gondii-infected animals, but eYFPhigh cells were restricted to different tissues. Highly eYFP fluorescent cells produced elevated levels of proinflammatory cytokines and chemokines in addition to IFN-
, suggesting their coregulated expression as a functional unit in highly differentiated effector T cells.
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