TABLE 1.

Possible mechanisms for T-cell apoptosis and immunosuppression after major trauma.

Pathway	Mechanisms	Comment	References
Cell-autonomous T cell death (ACAD)	• Intrinsic “caspase” pathway • Independent of death signals • Regulated by declining Bcl-2 at level of mitochondria • Cytochrome C released • Activates caspases • T cells undergo apoptosis without TCR restimulation	Toward the end of the immune response, activated lymphocytes not restimulated can die by permeabilizing the mitochondrial membrane. Bcl-2 is an anti-apoptotic protein that blocks the release of cytochrome c from mitochondria.	(53–55)
Stress-induced activation-induced cell death (AICD)	• Extrinsic “caspase” pathway • Death receptors: TNFR1, Fas, DR3, DR6, Trail-R1. • Glucocorticoid receptors (GRs) may also be involved • Receptor-driven apoptosis • Bax, bak, and BH3 domain • Activate caspases 8 and 3	A death receptor-mediated apoptosis pathway. The ligands for death receptors form a family of related cytokines collectively named as the TNF family.	(42, 52, 53, 56)
Monocyte-T cell interaction	• Extrinsic pathway • Inflammasome activation in monocytes sense DAMPs • IL-1β induced Fas-mediated monocyte driven T cell death via apoptosis	Monocytes sense injury-released DNA (DAMPs) via the AIM2 inflammasome and induce the extrinsic cell death of T cells.	(57)