© The Rockefeller University Press, 0022-1007/1997/2/461/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 3, February 3, 1997 461-470
Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells
Mercedes Rincón*,
Juan Anguita
,
Tetsuo Nakamura*,
,
Erol Fikrig
, and
Richard A. Flavell*,
From the * Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011;
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-9031; and
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011
Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon
trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.
Address correspondence to Dr. Richard A. Flavell, Section of Immunobiology, Yale University School of Medicine, PO Box 208011, New Haven, CT 06520-8011. M. Rincón's present address is the University of Vermont, Department of Medicine, Given Medical Bldg., Burlington, VT.
This work was supported by National Institutes of Health grants CA65861 and 1-P01-AI30548. R.A. Flavell is an investigator and T. Nakamura was an associate of the Howard Hughes Medical Institute. E. Fikrig is a Pew Scholar.
1 Abbreviations used in this paper: Cyt, cytochrome; NFAT, nuclear factor of activated T cells; RT, reverse transcriptase; WT, wild type.

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