CHANGES IN CELLS SUBSETS PRESENT IN THE THYMUS AFTER SYSTEMIC TH1 INFLAMMATORY/INFECTIOUS PROCESSES

NATALIA S. BAEZ ; FABIO M. CERBAN ; MARIA CECILIA RODRIGUEZ GALAN

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2013

We have demonstrated that during systemic inflammatory/infectious processes, peripheral mature T cells are able to enter the thymus. These cells could be distinguished from resident thymocytes based on the expression of high levels of the surface marker CD44. In this work we further characterized peripheral T cells residing in the thymus but also evaluated maturation changes that experience resident thymocytes during inflammatory/infectious Th1 processes. We found that resident SP (simple positive) thymocytes (CD44lo) are able to sense systemic inflammatory stimuli by changing its phenotype similar to mature T cells in secondary lymphoid organs (SLO). T cells found in SLO express high levels of Qa2 and low levels of CD24. In contrast, immature SP thymocytes expressed the opposite phenotype (Qa2lo-CD24hi). The inversion in the expression of these markers is expected to happen when recent thymic emigrants contact SLO, however, we observe that under certain Th1 systemic situations (LPS or IL-12+IL-18 in vivo or C. albicans and T. cruzi infections) SP thymocytes adopt the mature phenotype similar to a peripheral T cell (Qa2hi-CD24lo) (p<0.05, n=10-15). Regarding peripheral T cells that invade the thymus under these circumstances, we observed that they reside mainly in the thymic medulla (by IF staining) and that CD8+ CD44hi T cells expressed the transcription factor EOMES, characteristic of ?innate CD8 T cells? (p<0.05, n=8). Moreover, migration of the innate CD8+ T cells is an Ag-independent process probably driven by inflammatory mediators since CD8+ CD44hi EOMES+ T cells from OT-1 mice infected with T. cruzi (OVA is not expressed by the parasite) can also be found in the thymus between 10-14 days post-infection (p<0.05, n=5). All together, we conclude that the thymus is a target organ during systemic inflammatory/infectious processes being infiltrated by mature peripheral innate CD8+ T cells and altering the normal maturation of immature resident thymocytes.