IL4I1 Accelerates the Expansion of Effector CD8 + T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation

• Published in: Frontiers in immunology 2020-12, Vol.11, p.600012-600012
• Main Authors: Puiffe, Marie-Line, Dupont, Aurélie, Sako, Nouhoum, Gatineau, Jérôme, Cohen, José L, Mestivier, Denis, Lebon, Agnès, Prévost-Blondel, Armelle, Castellano, Flavia, Molinier-Frenkel, Valérie
• Format: Article
• Language: English
• Subjects: CD8 T cell; Immunology; immunosuppressive enzyme; Life Sciences; T cell immune response; T-cell activation; T-cell priming; viral infection
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.600012

IL4I1 is an immunoregulatory enzyme that inhibits CD8 T-cell proliferation and in the tumoral context. Here, we dissected the effect of IL4I1 on CD8 T-cell priming by studying the differentiation of a transgenic CD8 T-cell clone and the endogenous repertoire in a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. Unexpectedly, we show that IL4I1 accelerates the expansion of functional effector CD8 T cells during the first several days after infection and increases the average affinity of the elicited repertoire, supporting more efficient LCMV clearance in WT mice than IL4I1-deficient mice. Conversely, IL4I1 restrains the differentiation of CD8 T-cells into long-lived memory precursors and favors the memory response to the most immunodominant peptides. IL4I1 expression does not affect the phenotype or antigen-presenting functions of dendritic cells (DCs), but directly reduces the stability of T-DC immune synapses , thus dampening T-cell activation. Overall, our results support a model in which IL4I1 increases the threshold of T-cell activation, indirectly promoting the priming of high-affinity clones while limiting memory T-cell differentiation.