Abundant c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death. Blood 2009 Jul 30;114(5):1026-8
Date
05/12/2009Pubmed ID
19429865Pubmed Central ID
PMC2721783DOI
10.1182/blood-2009-03-210153Scopus ID
2-s2.0-70349229827 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
Activation-induced cell death (AICD) plays an important role in peripheral T-cell tolerance. AICD in CD4 T helper (Th) cells, including Th1 and Th2 effectors, has been extensively studied. Recently, interleukin-17-producing CD4(+) T cells (Th17 cells) have been identified as a unique Th subset, but their susceptibility to AICD and the underlying molecular mechanisms have not been defined. In this study, we found that Th17 cells were significantly less susceptible to AICD than Th1 cells, and Th17 cell resistance to AICD is due to the high levels of c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein preventing Fas-mediated apoptosis. The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy.
Author List
Yu Y, Iclozan C, Yamazaki T, Yang X, Anasetti C, Dong C, Yu XZAuthor
Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Cells, Cultured
Fas Ligand Protein
Genes, Reporter
Immune Tolerance
Immunization
Interleukin-17
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Ovalbumin
RNA, Small Interfering
Radiation Chimera
Specific Pathogen-Free Organisms
T-Lymphocytes, Helper-Inducer
Th1 Cells
bcl-X Protein