“Immune cells, and especially T cells, can’t work properly if they die too quickly – you want them to live and survive for long periods of time to be completely functional, in order to provide protection against whatever your immune system is reacting.  Part of what we do is to understand how proteins that are expressed on the surface of T cells affect the cell’s ability to live, to survive, and not to undergo apoptosis, which is the process of cell death,” said Michael Croft, Ph.D.

Apoptosis in one form is programmed cell death that is a natural part of the cell’s lifecycle and is often triggered once the cell has performed its primary function, for example in protecting the body from a threat.  Apoptosis can also be a regulated activity that is promoted by protein receptors on cells that directly induce death, and can represent a way of inhibiting an immune response, for example in favor of a pathogen or a cancer cell. Cell necrosis, on the other hand, is a traumatic cell death resulting from an acute cellular injury. 

T cells normally have a short lifespan.  There are processes in place that are required to limit the lifespan of a T cell -- negative suppressive influences as well as positive influences.  It would be unfavorable for these cells to be stimulated to respond to something and never die. The key lies in the balance between cell death and cell lifespan, and both are controlled by different proteins expressed on the surface of the cell.  The molecules that signal a T cells’ availability to respond also can determine how long the cell should live and whether it will die. 

In cancer, the logical goal is for the T cell to live longer, and in greater numbers than normal, so it can attack the tumor cell.  In autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, or in asthma, where the cells create an inappropriate or overactive immune response, the ideal is for the cell to respond more slowly or not at all.  In infectious disease, understanding apoptosis is key in the creation of vaccines that target viruses and bacteria, from Dengue virus to Cytomegalovirus (CMV), while leaving the body’s immune cells to flourish.  The implications for understanding apoptosis and cell death may even lead to cures for AIDS and Type 1 Diabetes. 

A focus of La Jolla Institute for Allergy & Immunology researchers is to understand what happens when certain cell proteins are triggered, and what happens within the cell that somehow either induces death, or otherwise affects the lifespan of the cell. In particular, Don Newmeyer, Ph.D. is examining how mitochondria--the "energy factory" in the cell-- play a critical role in the apoptotic cell death program. The importance of this research is in understanding how these cells can be turned on and off, suggesting new approaches for the treatment of diseases that involve the inappropriate death or survival of certain types of cells.