Development of innate T cells in the thymus under infectious/inflammatory systemic conditions

BAEZ N; SAVID FRONTERA C.; CERBAN F.; VOLPINI X.; MOTRÁN C.; RODRIGUEZ-GALÁN M. C.

Buenos Aires

Congreso; JOINT MEETING OF BIOSCIENCE SOCIETIES; 2017

Our previous work demonstrated that during the acute stage of certain infections with a strong Th1 component (Trypanosoma cruzi or Candida albicans), SP CD8 thymocytes alter their differentiation from ?conventional? to ?innate? lineage. Innate CD8+ cells express a particular phenotype (CD44hi CD122hi EOMEShi), produce high levels of IFN and have high cytotoxic activity. The switch in the SP CD8 lineage occurs by the inflammatory process since we obtained similar data when we induced systemic expression of IL-12 and IL-18 by hydrodynamic injection of their cDNAs. The aim of our work is to determinate the stage at which innate CD8+ T cells develop in the thymus and the molecular mechanisms that are involved in this differentiation. Our data demonstrate that the innate phenotype give rise as early as the double positive (DP) stage since when we co-cultured DP or SP CD8 CD45.1+ control thymocytes with CD45.2+ T. cruzi-infected thymocytes we observed that CD45.1+ cells adopt the mentioned innate features (p<0,05).The canonical Wnt/β-catenin signaling pathway is involved both in the differentiation of CD8 T cells and the generation of functional CD8 T cell memory. To investigate if this particular pathway is involved in the generation of innate CD8+ cells, we co-cultured CD45.1+ control thymocytes with CD45.2+ control or T. cruzi-infected thymocytes in the presence of Lithium chloride, an inductor of canonical Wnt pathway and we observed up-regulation of CD44 and EOMES regardless of the infection (p<0,05), while in the presence of iCRT, an inhibitor of β-catenin signaling, CD45.1+ control thymocytes down-regulate CD44 and EOMES in both control or infected conditions (p<0,05).The development of innate CD8+ T cells in the thymus under Th1 systemic processes may have implication in the output and the repertoire of T cells in secondary immune organs. Canonical Wnt pathway can be implicated in this deviation, but more experiments are necessary.