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Sharvan Sehrawat, Mitsuomi Hirashima, Barry Rouse, Regulation of virus-specific acute and memory CD8+ T cell response by Galectin-9/TIM-3 interaction (137.5), The Journal of Immunology, Volume 184, Issue Supplement_1, April 2010, Page 137.5, https://doi.org/10.4049/jimmunol.184.Supp.137.5
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Abstract
We demonstrate that galectin-9 (Gal-9) acts to constrain CD8+ T cell immunity to Herpes Simplex Virus (HSV) infection. In support of this, we show that animals unable to produce Gal-9, because of gene knockout, develop acute and memory responses to HSV that are of greater magnitude and better quality than those that occur in normal infected animals. Interestingly, infusion of normal infected mice with α-lactose, the sugar that binds to the carbohydrate-binding domain of Gal-9 limiting its engagement of T cell immunoglobulin and mucin (TIM-3) receptors, also caused a more elevated and higher quality CD8+ T cell response to HSV. Such sugar treated infected mice also had expanded populations of effector as well as memory CD8+ T cells. The increased effector T cell responses led to significantly more efficient virus control. The mechanisms responsible for the outcome of the Gal-9/TIM-3 interaction in normal infected mice involved apoptosis of TIM-3+ Teffectors as well as the promotion of Foxp3+ regulatory T cell activity. Our results indicate that manipulating galectin signals, as can be achieved using appropriate sugars, may represent a convenient and inexpensive approach to enhance primary and memory responses.
