CD8+ cytotoxic T lymphocytes (CTL) act as the effector arm of the cell -mediated immune system to kill undesirable cells. Two processes regulate these effector cells to prevent self reactivity. The first is a thymic selection process that largely eliminates auto -reactive clones,
Immunobiology 4th edition
the second regulation mechanism is in the form of a multistage activation process, also known as priming, that if successful endows them with a license to kill cognate target cells, or else they are fated to self destruct.
Charlotte Lahoute, Olivier Herbin, Ziad Mallat & Alain Tedgui, Nature Reviews Cardiology 8, 348-358
Hitherto no subsequent regulatory restrictions have been ascribed for properly primed and activated CTLs that are licensed to kill. We have shown hat CTLs possess a novel, post -priming regulatory mechanism(s) that influences the outcome of their encounter with cognate target cells. This mechanism gauges the degree of antigen density, whereupon reaching a certain threshold, significant changes occur which induce anergy in the effector T cells. The biological consequences of this antigen-induced post priming control includes alterations in the expression of cell surface molecules that control immunological synapse activity, cytokine profiles, and induce retarded cell proliferation. Most profound are genome-wide analysis which demonstrate changes in expression of genes related to membrane potential, T-cell receptor signal transduction, energy metabolism and cell cycle control. Thus, discernible and unique gene expression signature for anergy as a response to high antigen density has been observed.
Consequently, activated T cells possess properties of a self referential sensory organ. Our studies identify a new post -priming control mechanism of CTL with anergenic-like properties. This mechanism extends our understanding of the control of immune function and regulation such as peripheral tolerance, viral infections, anti tumor immune responses, hypersensitivity, and autoimmunity.
Currently, we are elucidating the molecular mechanisms and signal transduction pathways through which T cells can sense antigen density.