Immunity & infection

Oral

Metabolite Regulation of Human T Cell Immunity

Thursday, June 15
5:45 PM - 7:00 PM

T lymphocyte activation is regulated by the metabolism of glucose, fatty acids and amino acids, allowing the cell to meet increased energetic and biosynthetic demands. We previously determined that exogenous nutrient availability regulates the terminal differentiation of murine CD4+ T cells into distinct effector fates. Activation of naïve murine CD4+ T cells under conditions of glutamine deprivation causes them to terminally differentiate into Foxp3+ regulatory T cells (Treg) with potent in vivo suppressor function while blocking Th1 differentiation (Klysz et al., 2015). We now show that human CD4+ as well as CD8+ T cells are significantly more sensitive to extracellular glutamine than glucose, with deprivatio of the former resulting in a severely attenuated proliferation and defective upregulation of nutrient transporters. Furthermore, while the potential of T lymphocytes to secrete IL-2 is not markedly affected by glutamine deprivation, the secretion of IFNg is decreased by 5-10-fold. Notably, increasing intermediary glutamine metabolites in the tricarboxylic acid cycle significantly augments the potential of human T lymphocytes to transport extracellular nutrients, inhibiting Treg differentiation. Thus, nutrient availability and downstream metabolites can be used to modulate the T cell differentiation program and immune responsiveness.

Maria Matias

Graduate student
University of Montpellier/ Institut de Genetique Moleculaire de Montpellier

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    Gaspard Cretenet

    Institut de Genetique Moleculaire de Montpellier

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      Carmen Yong

      Institut de Genetique Moleculaire de Montpellier/ Peter MacCallum Cancer Center, Melbourne Australia

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        Cedric Mongellaz

        Institut de Genetique Moleculaire de Montpellier

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          Vincent Duriavic

          Institut de Genetique Moleculaire de Montpellier

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            Valerie Dardalhon

            Institut de Genetique Moleculaire de Montpellier

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              Naomi Taylor

              Institut de Genetique Moleculaire de Montpellier

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