Gfi-1 plays an important role in IL-2-mediated Th2 cell expansion.
Enforced expression of growth factor independent 1 (Gfi-1), a transcription repressor induced by T cell activation and IL-4/Stat6 signaling, strikingly enhances Th2 cell expansion. Using conditionally Gfi1-deficient mice prepared for this study, we show that in vitro or in vivo deletion of this factor dramatically reduces Th2, but not Th1, cell expansion in response to IL-2. Both increased cell apoptosis and reduced cell proliferation resulted from Gfi1 deletion. IL-2-Stat5 signaling was partially reduced in Gfi1-deficient Th2 cells, but overexpression of Stat5 failed to restore normal Th2 expansion in these cells, suggesting that Gfi-1 also functioned downstream of, or in parallel with, Stat5 signaling. Reduced Th2 cell expansion in the absence of Gfi-1 was confirmed by the diminished frequency of IL-4-producing cells when these mice were infected with Schistosoma mansoni.
Zhu
Jinfang
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jfzhu@niaid.nih.gov
Jankovic
Dragana
D
Grinberg
Alex
A
Guo
Liying
L
Paul
William E
WE
D000483:Alleles; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D007376:Interleukin-2; D050799:STAT5 Transcription Factor; D014157:Transcription Factors