Reversibility of T helper 1 and 2 populations is lost after long-term stimulation

doi:10.1084/jem.183.3.901

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Reversibility of T helper 1 and 2 populations is lost after long-term stimulation

E Murphy, K Shibuya, N Hosken, P Openshaw, V Maino, K Davis, K Murphy and A O'Garra
DNAX Research Institute, Palo Alto, California 94301-1104, USA.

Commitment of T helper 1 (Th1) or Th2 populations developing during an immune response to a pathogen, or an inappropriate immune response to an allergen or autoantigen, may determine the difference between health and chronic disease. We show that strongly polarized Th1 and Th2 populations assessed by immunoassay are heterogeneous using flow cytometry to detect single cells producing interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Th1 populations arising after 1 wk of stimulation in IL-12 plus anti-IL-4 antibodies could convert to Th2 cells when restimulated in IL-4. Th2 populations resulting from stimulation for 1 wk in IL-4 could give rise to Th1 cells upon restimulation in IL-12 plus anti-IL-4. In contrast, the cytokine profiles of long-term Th1 and Th2 populations arising originally from repeated stimulation in IL-12 or IL-4 appeared more homogeneous and were not reversible, although IL-4 dramatically reduced the number of IFN-gamma-producing Th1 cells. This may explain previous reports that Th1 cells can be converted to Th2 cells.
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Lee, H. J., O'Garra, A., Arai, K.-i., Arai, N. (1998). Characterization of cis-Regulatory Elements and Nuclear Factors Conferring Th2-Specific Expression of the IL-5 Gene: A Role for a GATA-Binding Protein. J. Immunol. 160: 2343-2352 [Abstract] [Full Text]
Shibuya, K., Robinson, D., Zonin, F., Hartley, S. B., Macatonia, S. E., Somoza, C., Hunter, C. A., Murphy, K. M., O'Garra, A. (1998). IL-1{alpha} and TNF-{alpha} Are Required for IL-12-Induced Development of Th1 Cells Producing High Levels of IFN-{gamma} in BALB/c But Not C57BL/6 Mice. J. Immunol. 160: 1708-1716 [Abstract] [Full Text]
Leonard, C., Tormey, V., Burke, C., Poulter, L. W. (1997). Allergen-induced Cytokine Production in Atopic Disease and Its Relationship to Disease Severity. Am. J. Respir. Cell Mol. Bio. 17: 368-375 [Abstract] [Full Text]
Lee, P. P., Zeng, D., McCaulay, A. E., Chen, Y.-F., Geiler, C., Umetsu, D. T., Chao, N. J. (1997). T Helper 2-Dominant Antilymphoma Immune Response Is Associated With Fatal Outcome. Blood 90: 1611-1617 [Abstract] [Full Text]
Kelso, A., Groves, P. (1997). A single peripheral CD8+ T cell can give rise to progeny expressing type 1�and/or type 2�cytokine genes and can retain its multipotentiality through many cell�divisions. Proc. Natl. Acad. Sci. USA 94: 8070-8075 [Abstract] [Full Text]
Lafaille, J. J., Keere, F. V. d., Hsu, A. L., Baron, J. L., Haas, W., Raine, C. S., Tonegawa, S. (1997). Myelin Basic Protein-specific T Helper 2 (Th2) Cells Cause Experimental Autoimmune Encephalomyelitis in Immunodeficient Hosts Rather than Protect Them from the Disease. JEM 186: 307-312 [Abstract] [Full Text]
Hu-Li, J., Huang, H., Ryan, J., Paul, W. E. (1997). In differentiated CD4+ T Cells, interleukin 4�production is cytokine-autonomous, whereas interferon gamma �production is�cytokine-dependent. Proc. Natl. Acad. Sci. USA 94: 3189-3194 [Abstract] [Full Text]
Szabo, S. J., Dighe, A. S., Gubler, U., Murphy, K. M. (1997). Regulation of the Interleukin (IL)-12R {beta}2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells. JEM 185: 817-824 [Abstract] [Full Text]