CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)–. In normal human spleens, the majority of CCR6+ memory T cells were in the close vicinity of CCR6+ myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6+ memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6+ T cells induced expression of IL-2, interferon-, CCL20, and CD40L, and autoreactive CCR6+ T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6+ T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions

CCR6 is expressed on an IL-10–producing, autoreactive memory T cell population with context-dependent regulatory function

Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)–β. In normal human spleens, the majority of CCR6+ memory T cells were in the close vicinity of CCR6+ myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6+ memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6+ T cells induced expression of IL-2, interferon-γ, CCL20, and CD40L, and autoreactive CCR6+ T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6+ T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions

Constructing legitimacy for climate change planning: A study of local government in Denmark

Within the literature, climate change mitigation and adaptation at the local level is in- creasingly portrayed as a new, discrete field of spatial planning research and practice. This article examines in detail the situated institutionalisation of this emerging field in local government in a specific case study context, Aarhus Municipality in Denmark. The concept of legitimacy is used as an analytical lens to examine institutionalisation patterns and practices. Based on a perspective grounded in new institutional theory, the research investigates how legitimacy affects the institutionalisation of climate change planning and how legitimacy is, in turn, affected by the interplay between agency and structure. The analytical foregrounding of the concept of legitimacy is concluded to generate ‘thicker’, more nuanced insights into why climate change planning practices take particular forms in specific contexts in terms of, for example, the role of networks external to local government, and the form of mitigation and adaptation activities. The results highlight the importance of what we label cultural-cognitive legitimacy (i.e. that derived from organisational rules and societal norms) in determining patterns and prac- tices of institutionalisation, whereas normative imperatives based on moral or ethical arguments are rarely invoked in relation to legitimacy. This indicates that the role of structures vis-a-vis agency (particularly in terms of the often cited case of institutional entrepreneurship) in relation to the institutionalisation of climate change planning with- in local government may be more complex than has been suggested much of the litera- ture. The predominance of cultural-cognitive over normative legitimacy also has im- portant implications for how discourses on climate change planning are framed. The implications of this for the nature of societal change that takes place in response to cli- mate change require further research attention