Challenge the paradigm of T cell memory and dissect its failure in preventing
Factors impeding effective T cell memory responses
Despite tremendous efforts, vaccines targeting pathogens that require T cell immune responses for control of disease, such as HIV, hepatitis C and TB, are effective. All our efficacious vaccines rely solely on B cell memory and antibody mediated immunity. Notwithstanding this, T cell memory remains the central dogma behind the development of vaccines for these diseases. The majority of immune memory work has been performed in mouse models were it is extremely difficult to dissect the relevance of T versus B cell memory in repeated challenge with the identical pathogen in the same host. Consequently, what appear to be effective memory T cell responses in the mouse have not translated to effective responses in humans. We take the unconventional view that a substantial failing is not a vaccines ability to prime a response but rather the inherent ineffectiveness of memory T cells in preventing disease. Using a novel model that does not interfere with T and B cell collaboration, we are dissecting the effectiveness of memory T cells alone and examine which host genes need to be manipulated to make a T cell response effective in a therapeutic setting.