IDM Dissertation Defense

Lyndsay Avery - PhD '18: Tim-3 co-stimulation promotes short-lived effector T cells, restricts...

Wednesday 4/25 9:00AM - 11:00AM
Scaife Hall

Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion

Abstract: Tim-3 is highly expressed on a subset of T cells during T cell exhaustion, in settings of chronic viral infection and 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 development of short-term effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3 deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, but may also contribute to exhaustion, by restricting development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is actually more similar to co-stimulatory receptors that are upregulated after T cell activation, rather than a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents. 

Mentor: Lawrence Kane, PhD (Mentor)
Advisor: Charles Rinaldo, PhD (Chair)

Last Updated On Friday, March 30, 2018 by Abby Kincaid
Created On Wednesday, March 07, 2018