What happens biologically in T cell exhaustion?

When there is an infection in the body, T cells work furiously to attack and completely eliminate the invading pathogen. In most cases, the T cells succeed. However, not all infections are easy to get rid of completely. When fighting off a challenging pathogen, the prolonged response can lead to T cell exhaustion, a phenomenon in which the T cells lose some of their functionality.  

Biologically, in T cell exhaustion, the immune system switches from trying to destroy the pathogen to learning how to manage it. The first action involves inhibiting T cells so they are unable to secrete proinflammatory messenger molecules (cytokines), and therefore cannot contribute much to an immune response. While T cells stay in this under-responsive state, they are not completely inert. Instead, they are partially responsive. Keeping T cells under control helps to keep the virus in check without causing too much collateral damage to the organism.

Although reversible, excessive T cell exhaustion can have considerable short- and long-term effects on the immune system. Excessive amounts of exhausted T cells can cause the body to be overcome with infection or permanently vulnerable to future infections. 

T cell exhaustion is a common occurrence in chronic diseases such as cancer, HIV, and Hepatitis C, in which a large number of T cells work for prolonged periods to prevent the spread of tumor cells or infection.