Dying to protect: cell death and the control of T‐cell homeostasis

Abstract

Summary T cells play a critical role in immune responses as they specifically recognize peptide/MHC complexes with their T cell receptors (TCRs) and initiate adaptive immune responses. While T cells are critical for performing appropriate effector functions and maintaining immune memory, they also can cause autoimmunity or neoplasia if misdirected or dysregulated. Thus, T cells must be tightly regulated from their development onward. Maintenance of appropriate T cell homeostasis is essential to promote protective immunity and limit autoimmunity and neoplasia. This review will focus on the role of cell death in maintenance of T cell homeostasis and outline novel therapeutic strategies tailored to manipulate cell death to limit T cell survival (eg autoimmunity and transplantation) or enhance T cell survival (eg vaccination, immune-deficiency).

Caspase-8 restricts antiviral CD8 T cell hyperaccumulation

“…1B). This pattern reinforces a role for CASP8 in restricting CD8 T cell expansion (30) without contributing to contraction, providing clarity to an area that has been extensively studied (8).…”

“…T cell numbers are regulated through intrinsic (mitochondrial) as well as extrinsic cell death pathways (8). Intrinsic apoptosis, regulated by Bcl-2 family members, has long been known to control the elimination of CD8 T cells in the thymus, during postthymic homeostasis, and throughout the robust expansion and contraction phases governing the response to foreign antigen (3,9,10).…”

Mitochondria as emerging targets for therapies against T cell acute lymphoblastic leukemia

“…Expanded clones of effector T cells are also eliminated by apoptosis during the terminal phase of immune response. All antiapoptotic BH1‐4 proteins, Bcl‐2, Bcl‐xL, Mcl‐1, and Bcl2A1 (known also as Bfl‐1 or A1), are involved in the T lymphocytes development and survival …”

“…37 Mcl-1, and Bcl2A1 (known also as Bfl-1 or A1), are involved in the T lymphocytes development and survival. [38][39][40] Primary B-and T-ALL cells overexpress antiapoptotic Bcl-2 proteins as a strategy to suppress apoptosis and promote survival. [41][42][43][44] To evade cell death and therapy, ALL may also decrease the expression of proapoptotic proteins (e.g., Bax), what may lead to a more complicated clinical scenario upon chemotherapy.…”

Cell death and the immune system: getting to how and why

“…address how apoptosis in the thymus shapes the immune repertoire, functioning in each step of the selection process. Li, et al . and Zheng, et al .…”