Fueling T Cell in Immunity

Thursday, June 15
10:30 AM - 11:00 AM

Lymphocyte activation leads to rapid proliferation and differentiation and we have shown that CD4 T cell subsets are metabolically distinct. The effector T cell fates (Th1, Th2, Th17) activate a highly glycolytic program. Regulatory T cells (Treg), in contrast, utilize a more oxidative metabolism and utilize lipids as a major fuel. These metabolic distinctions may allow new understanding and approaches to manipulate immunity. Glut1 is a member of the glucose transporter family, of which T cells express several members. We have shown that while effector T cells require Glut1 and aerobic glycolysis to promote immunity, Treg can function independent of Glut1 to suppress Inflammatory Bowel Disease (IBD). We have examined the metabolism of Treg in detail and found that FoxP3 itself can promote oxidative metabolism characteristic of Treg and that this is critical to maximize Treg suppressive capacity. Treg can be glycolytic and proliferative in vivo. We found, however, that glucose uptake and glycolysis impaired Treg stability and led to reduced protection against IBD. Thus Treg regulate glycolytic and oxidative metabolism to balance proliferation and suppressive function. Effector T cells were also found to be metabolically suppressed in clear cell Renal Cell Carcinoma (ccRCC), where glucose uptake and mitochondrial defects impaired CD8 T cell activation. Understanding mechanisms that regulate T cell metabolism may provide new tools to modulate immunity the balance of T cell effector and regulatory populations.

Learning Objectives:

Jeff Rathmell

Vanderbilt University Medical Center

Dr. Rathmell studies mechanisms that influence lymphocyte death and differentiation in inflammatory diseases and cancer. Following undergraduate studies at the University of Northern Iowa, his earned a PhD in Immunology at Stanford University. In postdoctoral studies at the University of Chicago and University of Pennsylvania, he showed that lymphocyte metabolism was dynamically regulated to control cell function and survival in inflammatory diseases and cancer. He began at Duke University in 2003 in the departments of Pharmacology and Cancer Biology and Immunology and moved in 2015 to Vanderbilt University to direct the Vanderbilt Center for Immunobiology and co-leads to Host Tumor Interactions Program of the Vanderbilt Ingram Cancer Center. The ongoing focus on Dr. Rathmell’s ongoing work is to understand how metabolic pathways regulate CD4 T cell subsets in inflammatory diseases and how the tumor microenvironment and metabolism impacts anti-cancer responses.


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