Cytotoxic T lymphocytes play a crucial role in adaptive immunity, primarily defending against tumors and viruses. These cells develop within the thymus gland and undergo rapid activation upon encountering an antigen.
Some T-cells also form memory T lymphocytes, which are affected by in vivo environments and host factors. Understanding the molecular basis of exhausted and memory T lymphocytes is essential to develop cell-mediated immunity-based interventions.
In a recent review published in Cellular & Molecular Immunology, researchers describe molecular signaling regulated by mammalian target of rapamycin (mTOR), especially mTOR complex 2 (mTORC2), among memory and exhausted cytotoxic cluster of differentiation 8-expressing (CD8+) T lymphocytes.
Study: Regulation of CD8+ T memory and exhaustion by the mTOR signals. Image Credit: fusebulb / Shutterstock.com
Integration of cellular metabolic pathways by mTOR and mechanisms underlying T lymphocyte exhaustion
Cytotoxic T cells (CTLs) differentiate to form effector cells in acute infections and memory cells for durable immune protection. In chronic infections and cancer, CTLs progressively differentiate into a dysfunctional exhaustive state.
The immune system’s complex nature is highlighted by the heterogeneous pools of exhausted and memory CTLs. Chronic antigen stimulation and inflammation can lead to T-cell exhaustion, which is characterized by loss of effector function and expression of multiple inhibitory receptors.
T-cell receptor (TCR) stimulation is the major cause of T lymphocyte exhaustion, with exhausted (Tex) cells constituting a unique cytotoxic subset. Tex