Based on this data, it is surprising that the possibility that the entrance of mature cells into the thymus could be a common occurrence during the acute phase of an infectious/inflammatory process has not been generally addressed, since a large proportion of T and B cells acquire an activated phenotype in these situations. Moreover, thymocyte depletion observed in
several infectious disease models could even increase the possibility of peripheral cell migration into the thymus considering reports describing Palbociclib mouse that when the cellularity of this organ is compromised (neonatal, irradiation, SCID mice, atrophic aged thymi, etc.), peripheral cell infiltration into the thymus considerably increases [4, 6, 18, 19]. In this context, the aim of this work is to demonstrate Metformin that migration of peripheral T and B cells
to the thymus occurs during the early phase of Th1 inflammatory/infectious processes triggered by different type of pathogens. In support of this hypothesis, we examine the entrance of B and T cells into the thymus in well-established Th1 infectious/inflammatory murine models. Furthermore, we demonstrate that peripheral T cells and B cells but not NK cells, macrophages, or DCs largely migrate to the thymus under inflammatory/infectious conditions but only when the cellularity of the organ is compromised. Moreover, the entrance of peripheral lymphocytes to the thymus necessarily requires monocyte chemoattractant protein-1 (MCP-1) production in this Pyruvate dehydrogenase lipoamide kinase isozyme 1 organ and CCR2 expression
on migrating lymphocytes. Importantly, we demonstrate as a general mechanism that this phenomenon is triggered by IL-12 and IL-18 produced during the acute phase of Th1/inflammatory/infectious processes. Moreover, our data with OVA-specific TCR transgenic mice suggest that rather than being a TCR-dependent mechanism, any T cell has the potential to migrate to the thymus in response to inflammatory conditions. To address if migration into the thymus of mature peripheral lymphocytes is a common feature of Th1-driven inflammatory/infectious processes, we adoptively transferred CFSE-labeled splenocytes from mice either treated in vivo with LPS (a bacterial product) or infected with a fungus (Candida albicans) or a parasite (Trypanosoma cruzi) to recipient hosts that have received the same treatments. All these pathological conditions are characterized by a potent Th1 immune response, especially during the acute phase of the process [20-23]. Data presented in Fig. 1 demonstrate that after LPS treatment (Fig. 1A), C. albicans (Fig. 1B), or T. cruzi (Fig. 1C) infections, CD4+ and CD8+ T cells together with B cells entered the thymus in different proportions.