Aberrant expression of Fas ligand in mice deficient for the MHC class II transactivator.
The MHC class II transactivator (CIITA) is a critical regulator of MHC class II genes and other genes involved in the Ag presentation pathway. CIITA-deficient mice lack MHC class II expression on almost all APCs. In this study, we show that these mice also have aberrant Fas ligand expression on both CD4 T cells and B cells. We found that Fas ligand expression was greatly increased on CIITA-deficient CD4 T cells during the Th1 differentiation process. However, both CIITA-deficient and control Th1 effector cells up-regulated Fas ligand to similar levels if cells were reactivated. The introduction of CIITA into primary CD4 T cells via retroviral infection resulted in a reduction in the level of Fas ligand and delay in apoptosis after activation. Interestingly, activated B cells from the CIITA-deficient mice also showed increased levels of Fas ligand that could be to some degree inhibited by the introduction of IL-4.
Gourley
Tania S
TS
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Patel
Dipak R
DR
Nickerson
Kevin
K
Hong
Soon-Cheol
SC
Chang
Cheong-Hee
CH
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C083728:MHC class II transactivator protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators