Signaling Requirements for the Generation of CD8 T Cell Memory

The immune system has a remarkable ability to remember its previous encounters with a specific pathogen. Upon re-exposure to a pathogen, the immune system reacts at an accelerated rate and controls the invading pathogen expeditiously. The ability of the immune system to remember prior encounters is termed “Immunological Memory”, which is due to induction of memory T and B cells. Although induction of T and B cell memory is the basis of vaccination, the molecular mechanisms that govern the quantity, quality, and duration of memory-dependent protective immunity are not well understood.

CD8 T cells also known as cytotoxic T cells play an important role in defense against viruses, intracellular bacteria and protozoa. Therefore, there is an impetus to develop vaccines that engender potent and enduring CD8 T cell memory against these intracellular pathogens. Protective immunity against intracellular pathogens depends upon the quantity and quality of memory CD8 T cells. Research in our laboratory is focused on understanding the molecular mechanisms that govern the number and quality of memory CD8 T cells.

Acute viral infections often induce potent CD8 T cell responses and immunity that lasts for the life of an individual. Uncovering the mechanisms that govern the establishment and maintenance of CD8 T cell memory to acute viral infections would be expected to foster the development of strategies to develop vaccines that induce durable CD8 T cell-dependent protective immunity. The constellation of signals acting on the CD8 T cells during the activation and expansion phase of the T cell response programs the survival and differentiation of memory CD8 T cells. The Akt signaling pathway plays a crucial role in controlling the differentiation and cell fate in many cell types. Our laboratory is particularly interested in deciphering the role of

1. Akt/FoxO/mTOR signaling cascade in programming CD8 T cell memory to acute viral infections

2. CDK inhibitor p27Kip1 in regulating differentiation of memory CD8 T cells.