There are a number of issues in this study that still must be clarified

trongly influence this regulatory pathway. With this regard, it was interesting to find out whether TB-susceptible I/St differ from TB-resistant B6 mice by the content of Treg cells during chronic TB infection. To address this issue, we estimated the content of CD4+CD25+Foxp3+ cells along slowly progressing TB infection in mediastinal lymph nodes which drain the lungs. As shown in Discussion As emphasized in a recently published review, there are large gaps in our knowledge regarding the identity of regulatory DC. It is not clear whether regulatory DC are terminally differentiated cells or represent a transient functional state of a more general DC population triggered by the contact with stroma in an environment of organs. In particular, more should be learned about modulation of stromal cell function by pathogens and inflammatory reactions to consider therapeutic strategies aimed at DC manipulation. So far, shifts in instructive activity of stromal cells regarding immature DCreg development during host-parasite interactions were demonstrated only for leishmania and helminth invasions. We add intracellular mycobacterial pathogens to this list by demonstrating that TB infection differentially affects instructive capacity of lung stroma in genetically TB-susceptible and resistant mice, and that the developing DCreg directly down-regulate the response of mycobacteria-specific CD4+ T lymphocytes. Our findings demonstrate 9057848 that both major cell populations functioning as down-regulators of superfluous T cell immune responses, DCreg and Treg, were more readily developed and more efficiently maintained in mice displaying less severe lung 181223-80-3 inflammation and pathology in the course of TB infection. These results are in good agreement with those recently published by Leepiyasakulchai et al. who demonstrated similar correlations between the numbers of regulatory dendritic and T cells in the lung, genetic susceptibility to TB challenge and degree of lung pathology. Importantly, their observations concerned a different population of regulatory DC, namely, anti-inflammatory CD103+CD11b-CD11c+ E-DC, whereas in our study we characterized immature CD11b + CD103- DCreg educated on lung stroma. Yet another example of pneumonic phagocyte’s involvement in immune response inhibition which depends upon mycobacterial infection is an enhanced production of TGF- and PGE2 by pleural macrophages following engulfment of BCG-infected apoptotic neutrophils. Given that the macrophage-rich lung stroma itself is able to directly inhibit T-cell immune responses to several infectious and polyclonal stimuli, we may conclude that a redundancy in the T cell responses suppression system is an essential feature of the lung tissue functioning. This is not surprising, since maintenance of the 5 Regulatory DC in Experimental TB balance between cellular immune responses-mediated protection and pathology is critical for successful regulation of overwhelming inflammation affecting mucosal organs during chronic pathologic conditions, such as TB and IBD. Whereas cell populations participating in inhibition of immune responses and inflammation in the lung are impressively diverse, the number of soluble mediators providing suppression which are produced by these cells is small. Production of antiinflammatory cytokine IL-10 is a feature conserved among virtually all systems in which activity of immune response inhibitory cells, such as different regulatory 1717682 DC and Foxp3+ Treg, has been studi