TY - JOUR
T1 - Developmental commitment to the Th2 lineage by extinction of IL-12 signaling
AU - Szabo, Susanne J.
AU - Jacobson, Nile G.
AU - Dighe, Anand S.
AU - Gubler, Uell
AU - Murphy, Kenneth M.
N1 - Funding Information:
We thank Drs. E. Unanue, R. Schreiber. and C. Tripp for reagents and helpful discussions; Drs. B. Drucker, J. Darnell, and J. O’Shea for valuable antibodies; and P. Chand for FACS sorting. This work was supported by National Institutes of Health grants Al31236 and Al34560, and grant from the Monsanto Corporation.
PY - 1995/6
Y1 - 1995/6
N2 - Developmental commitment to Th1 or Th2 responses critically Influences host susceptibility to particular pathogens. We describe a novel mechanism governing stable commitment to Th2 differentiation. Naive T cells develop strongly polarized Th1 and Th2 profiles by 7 days after activation. However, commitment of these developing cells differs substantially. Although IL-4 reverses early Th1 differentiation, IL-12 cannot reverse early Th2 differentiation. Th1 reversibility results from maintenance of IL-4 signal transduction, whereas Th2 commitment results from rapid loss of IL-12 signaling. The IL-12 signaling defect in Th2 cells results in failure to phosphorylate Jak2, Stat3, and Stat4. Since Th2 cells express the mRNA for the cloned murine IL-12 receptor β subunit, the signaling defect may Involve expression or function of unidentified receptor components. The rapid extinction of IL-12 signaling in Th2 cells provides a demonstration of a mechanism for the stable commitment to a T helper phenotype.
AB - Developmental commitment to Th1 or Th2 responses critically Influences host susceptibility to particular pathogens. We describe a novel mechanism governing stable commitment to Th2 differentiation. Naive T cells develop strongly polarized Th1 and Th2 profiles by 7 days after activation. However, commitment of these developing cells differs substantially. Although IL-4 reverses early Th1 differentiation, IL-12 cannot reverse early Th2 differentiation. Th1 reversibility results from maintenance of IL-4 signal transduction, whereas Th2 commitment results from rapid loss of IL-12 signaling. The IL-12 signaling defect in Th2 cells results in failure to phosphorylate Jak2, Stat3, and Stat4. Since Th2 cells express the mRNA for the cloned murine IL-12 receptor β subunit, the signaling defect may Involve expression or function of unidentified receptor components. The rapid extinction of IL-12 signaling in Th2 cells provides a demonstration of a mechanism for the stable commitment to a T helper phenotype.
UR - http://www.scopus.com/inward/record.url?scp=0029071483&partnerID=8YFLogxK
U2 - 10.1016/1074-7613(95)90011-X
DO - 10.1016/1074-7613(95)90011-X
M3 - Article
C2 - 7796298
AN - SCOPUS:0029071483
SN - 1074-7613
VL - 2
SP - 665
EP - 675
JO - Immunity
JF - Immunity
IS - 6
ER -