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Mechanisms of Oral Tolerance: Regulatory T Cells—Summary of Part III

This discussion followed talks by Andrew Caton, Warren Strober, Fiona Powrie, Manuela Battaglia, and Richard Blumberg on various aspects of regulatory cell function. Meeting organizer Lloyd Mayer kicked off the session by pointing out that regulatory cells form a large grouping. Rather than comprising just one population, there is a wide panoply of regulatory cells in the body. Mayer posed a series of questions to the panel: Is there crosstalk between different types of regulatory cells? Which are most important? Are there organ specificities? Are there unique features about the ways in which investigators are activating/isolating regulatory cells in vitro or in vivo that obscure their real function in vivo? Although much current interest is focused on regulatory CD4+CD25+ T cells, Mayer pointed out that depletion of these “natural” CD4+CD25+ regulatory T (Treg) cells by neonatal thymectomy leads to autoimmune gastritis, not colitis or other forms of autoimmunity, suggesting organ specificity in Treg cell generation and/or function. Mayer asked each of the session’s speakers to attempt to describe their view of the particular type of regulatory cell they study in its in vivo context. Manuela Battaglia said that Tr1 are antigen specific, and are induced in the periphery after chronic exposure to antigen in the presence of IL-10. Tr1 can be generated from CD25− T cells but it is not known if they talk to, or are dependent on, CD25+ T cells. By contrast, CD4+CD25+ T cells are natural noninduced Treg cells that are present at birth. Warren Strober agreed with Dr. Battaglia and emphasized that, in most instances, Tr1 cells are induced by exogenous microbial antigen and generated locally, not at the level of the thymus. By contrast, CD4+CD25+ Treg cells are directed at self-