How Does the Immune System Develop Memory?

The immune system has the ability to recognize bacteria and viruses it has encountered in vaccines. How? The efficacy of vaccines depends on strong, long-term development of immune memory. A type of white blood cell, the CD8+ T cell, is especially good at killing infected cells. The development of memory CD8+ T cells, cells that remember antigens and trigger more CD8+ T cell production, can therefore influence how well or how poorly the immune system responds to threats. If researchers were able to selectively manipulate the development of these memory CD8+  T cells, they could tune the immune response under specific conditions. There’s one problem: the process for how memory CD8+  T cells are formed is poorly understood.

Avery August, Microbiology and Immunology, is working to uncover the nuances of cell signaling that lead to the production of these critical cells. Memory CD8+  T cells develop after antigenic responses over the duration of several identifiable phases. Initial antigen or pathogen recognition initiates the expansion of naive T cells, which develop into effector T cells. When the pathogen or antigen is cleared, the effector T cells undergo a drastic contraction phase, with the death of a majority of the effector cells and the development of memory precursor effector cells, which then differentiate into memory T cells. Three parameters that affect these responses are antigen affinity, T cell receptor (TcR) signal strength and inflammation. How these parameters intersect to control memory development is unclear.

August’s preliminary data suggest that a protein, tyrosine kinase (Itk), tunes T cell-mediated inflammation and the timing of the CD8+ memory T cell response. The August lab is continuing to determine the role that Itk plays in the development of CD8+ effector and memory responses during bacterial infection. This work will provide information on a signaling pathway that could be manipulated to enhance the development of memory T cells, while reducing vaccine-induced inflammation.

The work in August’s lab could lead to a method for tuning the development of CD8+ T cell memory in humans. NIH Award Number: 1R01AI120701-01  

Cornell Researchers

Funding Received

$1.5 Million spanning 4 years