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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

Recent Dissertations

IDM Dissertation Defense
Lyndsay Avery - PhD '18: Tim-3 co-stimulation promotes short-lived effector T cells, restricts... IDM Dissertation Defense
Lyndsay Avery - PhD '18: Tim-3 co-stimulation promotes short-lived effector T cells, restricts...
Wed 4/25/2018 9:00AM - 11:00AM
Scaife Hall

Lyndsay Avery's Dissertation, Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion, includes findings that have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents. 


IDM Dissertation Defense
Parichat Duangkhae - PhD '18: Defining Dengue Virus Infection in Human Skin IDM Dissertation Defense
Parichat Duangkhae - PhD '18: Defining Dengue Virus Infection in Human Skin
Tue 4/3/2018 2:00PM - 4:00PM
Public Health Lecture Hall (A115)

Parichat Duangkhae's Dissertation, Defining Dengue Virus Infection in Human Skin, may provide a mechanism for the epidemiologic observation that African ancestry protects against severe dengue. Her findings highlight the importance of skin and the complex interplay between resident and immune skin cell populations in DENV infection and dengue pathogenesis.


IDM Dissertation Defense
Diana Campbell Delucia - PhD '18: Cellular cholesterol regulation of HIV-1 trafficking during... IDM Dissertation Defense
Diana Campbell Delucia - PhD '18: Cellular cholesterol regulation of HIV-1 trafficking during...
Thu 3/1/2018 11:00AM - 1:00PM
Public Health Lecture Hall (A115)

Diana's dissertation, Cellular cholesterol regulation of HIV-1 trafficking during macrophage-mediated trans infection, suggests that targeting the ability of MΦ to drive HIV-1 dissemination in trans could significantly enhance HIV-1 therapeutic strategies. 


IDM Dissertation Defense
Ben Policicchio - PhD '17 IDM Dissertation Defense
Ben Policicchio - PhD '17
Thu 12/7/2017 11:00AM - 1:00PM
Public Health Lecture Hall (A115)

Ben's dissertation, Use of Integrase Inhibitor to Assess the Cytotoxic T Lymphocyte Response During Simian Immunodeficiency Virus Infection in Rhesus Macaques, hopes to aid in the hunt for an elusive vaccine and/or cure against HIV by showing CD8+ cells kill cells containing virus prior to integration.


IDM Dissertation Defense
Zach Swan - PhD '16 IDM Dissertation Defense
Zach Swan - PhD '16
Fri 12/9/2016 2:00PM - 4:00PM
A216 Public Health

Zachary Swan of IDM presents a PhD Dissertation Defense entitled "Contributions of Macrophages in Lymph Nodes and Gut Mucosa to SIV Disease Control and Progression”


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