Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion

Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion

In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimate...

SnapShot: T Cell Exhaustion

Recent Advances in T Cell Signaling in Aging

The immune system of mammalian organisms undergoes alterations that may account for an increased susceptibility to certain infections, autoimmune diseases, or malignancies. Well characterized are age related defect in T cell functions and cell mediated immunity. Although it is well established that the functional properties of T cells decrease with age, its biochemical and molecular nature is...

Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton

Using antigen-specific T cell clones and peptide-pulsed antigen-presenting cells (APCs) we investigated the mechanisms that lead to sustained signaling, known to be required for activation of effector function. Four lines of evidence indicate that the T cell actin cytoskeleton plays a crucial role in T cell activation by antigen-pulsed APCs, but is not required when T cell receptor (TCR) is cro...

Inhibitory Receptors Beyond T Cell Exhaustion

Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing -unprecedented results in the treatment of cancer patients. Consequently, the clinical potential in this field is broad, calling for inc...