@unpublished{pittir34548,
           month = {September},
           title = {Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion},
          author = {Lyndsay Avery},
            year = {2018},
        keywords = {T cell exhaustion
LCMV
chronic infection
mTOR
T cells
Tim-3
immunotherapy},
             url = {http://d-scholarship-dev.library.pitt.edu/34548/},
        abstract = {Tim-3 is highly expressed on a subset of T cells during T cell exhaustion, in settings of chronic viral infection and in tumors. Using LCMV Clone 13, a model for chronic infection, we have found that Tim-3 is neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted the development of short-term effector T cells, at the expense of memory precursor development, following acute infection with LCMV-Armstrong. These effects were accompanied by increased Akt/mTOR signaling in T cells with endogenous or ectopically expressed Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3 deficient mice. Thus, Tim-3, while essential for optimal effector T cell responses, but may also contribute to T cell exhaustion is restricting the development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is more similar to co-stimulatory receptors that are upregulated following T cell activation, rather than dominant inhibitory proteins such as PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as immunotherapy agents for the treatment of cancer, infections, and other matters of public health.}
}