Desarrollo de células T innatas en timo bajo condiciones infecciosas/inflamatorias sistémicas

BAEZ NATALIA SOLEDAD; SAVID FRONTERA CONSTANZA; CERBÁN FABIO; MARIA CECILIA RODRIGUEZ-GALAN

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXIV REUNIÓN ANUAL Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Our previous work demonstrated that during the acute stage of certain infections (Trypanosoma cruzi or Candida albicans) with a strong Th1 component, the number of CD8+CD44hi T cells in the thymus increased. These cells are named ?innate T cells? and belong to a different lineage from conventional SP CD8 thymocytes that give rise in the thymus. They express the transcription factor EOMES, produce high levels of IFN and differentiate in the presence of IL4 and IL15. This effect is mediated by the inflammatory process since we obtained similar data when we induced systemic expression of IL12 and IL18 by hydrodynamic injection of their cDNAs. The aim of our work is to determinate the origin and function of these cells. Our flow cytometry data demonstrated that these cells express the killing receptor NKG2D and have high cytotoxic activity measured by CD107a expression assay (p<0,05).Moreover, when mice are adoptively transferred with thymocytes from OT-I T. cruzi-infected or IL12 + IL18-treated mice previous to T. cruzi infection, a protective effect can be observed since the overall survival is increased and parasitemia is decreased compared to non-transferred control mice (p<0,05).When we injected CD45.1+ control thymocytes directly into the thymuses of T. cruzi-infected CD45.2+ mice, we observed that CD45.1+ cells up-regulated CD44 and EOMES expression compared to CD45.1+ cells injected in non-infected CD45.2+ recipient mice (p<0,05). Moreover, when we co-cultured CD45.1+ control thymocytes whit CD45.2+ T. cruzi-infected thymocytes we observed up-regulation of CD44 and EOMES in a IL4 and IL15-dependent manner (p<0,05).Our results indicate that under systemic infectious/inflammatory processes, innate CD8+ T cells are generated in the thymus by local IL4 and IL15 production. The presence of non-conventional CD8+ T cells suggests a deviation in the normal thymic ontogeny that may have implication in the output and the repertoire of T cells in secondary immune organs.