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The Journal of Immunology, 2005, 174: 7732-7739.
Copyright © 2005 by The American Association of Immunologists

The Functional Heterogeneity of Type 1 Effector T Cells in Response to Infection Is Related to the Potential for IFN-{gamma} Production1

Katrin D. Mayer*, Katja Mohrs*, Sherry R. Crowe*, Lawrence L. Johnson*, Paul Rhyne{dagger}, David L. Woodland* and Markus Mohrs2,*

* Trudeau Institute, Saranac Lake, NY 12983; and {dagger} Upstate Biotechnology, Lake Placid, NY 12946

The expression of IFN-{gamma} 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-{gamma}, 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-{gamma}-enhanced yellow fluorescent protein (IFN-{gamma}-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-{gamma} 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-{gamma} transcripts and the secretion of IFN-{gamma} upon stimulation. CD4+ and CD8+ T cells of influenza-infected mice revealed a similarly heterogeneous IFN-{gamma} 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-{gamma}, suggesting their coregulated expression as a functional unit in highly differentiated effector T cells.




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