Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim
Kapoor, Varun N.
Kennedy, Norman J.
Edwards, Yvonne J. K.
Welsh, Raymond M.
Davis, Roger J.
Brehm, Michael A.
Document TypeJournal Article
MetadataShow full item record
AbstractApoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Loss of Fas and Bim function in Bcl2l11(-/-)Fas(lpr/lpr) mice inhibited apoptosis of T cells and prevented the early T cell attrition resulting from lymphocytic choriomeningitis virus infection. Bcl2l11(-/-)Fas(lpr/lpr) mice were also resistant to prolonged allograft survival induced by CoB targeting the CD40-CD154 pathway. These results demonstrate that both extrinsic and intrinsic apoptosis pathways function concurrently to regulate T cell homeostasis during the early stages of immune responses and allograft survival during CoB.
J Immunol. 2019 Feb 1;202(3):647-651. doi: 10.4049/jimmunol.1800278. Epub 2019 Jan 4. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44379