Either IL-2 or IL-12 is sufficient to direct Th1 differentiation by nonobese diabetic T cells.
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-gamma-producing Th1 cells in response to polyclonal TCR stimulation in the absence of IL-12 and IFN-gamma. 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-gamma-producing autoreactive T cells.
Zhou
Weisong
W
Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Zhang
Feng
F
Aune
Thomas M
TM
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma