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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/19180

Title: Analysis of Adipose CD4+ TCR alpha/beta T cells in Obesity-associated Insulin Resistance
Authors: Chan, Yin
Advisor: Dosch, Hans-Michael
Department: Immunology
Keywords: Obesity
T cells
Issue Date: 1-Mar-2010
Abstract: Progressive obesity and its associated metabolic syndromes represent a globally growing challenge, yet mechanistic understanding and current therapeutics are unsatisfactory. We discovered that CD4+ T-lymphocytes, resident in visceral adipose tissue (VAT), control insulin-resistance in diet-induced obese (DIO) mice and likely humans. DIO VAT-associated T cells display biased TCR-Valpha/betarepertoires suggesting antigen-specific expansion. CD4+ T-lymphocyte control of glucose homeostasis is compromised in DIO when VAT accumulates pathogenic IFNgamma-secreting Th1 cells, overwhelming static numbers of Th2 (CD4+GATA-3+) and regulatory Foxp3+ T cells. CD4+ T cell transfer into DIO, lymphocyte-free RAGnull mice reversed weight gain and insulin resistance predominately through Th2 cells. Brief systemic treatment with anti-CD3 antibody or its F(ab’)2 fragment, restores the Th1/Foxp3+ balance and reverses insulin resistance for months, despite continuing high-fat diet. CD4+ T cells impact the progression of obesity-associated metabolic abnormalities and can be manipulated by immunotherapy.
URI: http://hdl.handle.net/1807/19180
Appears in Collections:Doctoral
Department of Immunology - Doctoral theses

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