Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim
Program in Molecular Medicine; Department of Pathology; Davis Lab
Hemic and Immune Systems | Immunology and Infectious Disease
Apoptosis 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.
DOI of Published Version
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
Journal of immunology (Baltimore, Md. : 1950)
Jangalwe, Sonal; Kapoor, Varun N.; Xu, Jia; Girnius, Nomeda; Kennedy, Norman J.; Edwards, Yvonne J. K.; Welsh, Raymond M.; Davis, Roger J.; and Brehm, Michael A., "Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim" (2019). Program in Molecular Medicine Publications and Presentations. 107.