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Either IL-2 or IL-12 Is Sufficient to Direct Th1 Differentiation by Nonobese Diabetic T Cells¹

Weisong Zhou^*, Feng Zhang^* and Thomas M. Aune^2,*,

^* Division of Rheumatology, Department of Medicine, and Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232

Th cell differentiation from naive precursors is a tightly controlled process; the most critical differentiation factor is the action of the driving cytokine: IL-12 for Th1 development, IL-4 for Th2 development. We found that CD4⁺ T cells from nonobese diabetic mice spontaneously differentiate into IFN--producing Th1 cells in response to polyclonal TCR stimulation in the absence of IL-12 and IFN-. Instead, IL-2 was necessary and sufficient to direct T cell differentiation to the Th1 lineage by nonobese diabetic CD4⁺ T cells. Its ability to direct Th1 differentiation of both naive and memory CD4⁺ T cells was clearly uncoupled from its ability to stimulate cell division. Autocrine IL-2-driven Th1 differentiation of nonobese diabetic T cells may represent a genetic liability that favors development of IFN--producing autoreactive T cells.

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