Suppression of T-cell activation triggered by weak stimuli. Regulation of the effector class of the immune response. Suppression of pathogen-induced immunopathology. Induction of maternal tolerance to the fetus. Induction of tolerance against dietary antigens, i.e. Prevention of autoimmune diseases by establishing and maintaining immunologic self-tolerance. virus-specific) Th cells which should not? self-reactive) Th cells, which should be suppressed, and the good (i.e.
(A) What are the functions of Treg cells? (B) What molecular markers can be used to distinguish Treg cells from conventional Th cells? (C) Do Treg cells recognize self or non-self? (D) Do Treg cells represent a distinct lineage of CD4 + T cells? (E) How do Treg cells know which Th cell to suppress? In other words, how do Treg cells discriminate between the bad (i.e.
I also would like to encourage all readers interested in immunologic controversies to read and send contributions to the discussion forum of the Scandinavian Journal of Immunology. My main objective is to briefly summarize the current knowledge in the Treg field and to define some key questions which remain to be answered. The present review will focus on CD4 + Treg cells and will not discuss the older literature on the functionally-related suppressor T cells. However, many central aspects of Treg cell biology remain obscure and hotly debated. Treg cells represent nowadays a large field of research and a long list of Treg-associated suppressive mechanisms have been reported. Treg cells are defined as T cells in charge of suppressing potentially deleterious activities of Th cells. Conventional Th cells control the adaptive immunity by activating, in an antigen-specific fashion, other effector cells such as CD8 + cytotoxic T cells, B cells and macrophages. Accordingly, CD4 + T cells are now commonly divided into two distinct lineages: Treg cells and conventional T helper (Th) cells. In the mid-1990s, a new subpopulation of suppressor T cells was proposed which expressed CD4 and which was named regulatory T (Treg) cells. In fact, the concept of suppressor T cells was largely abandoned by the end of the 1980s, essentially because of the poor characterization of the cells and the lack of specific markers. However, the existence of suppressor T cells as a distinct lineage of T cells has been very controversial. Suppressor T cells, which were characterized by expression of the CD8 (Lyt-2) cell surface marker, have been the topic of more than 1000 scientific publications. Already in the early 1970s, it was proposed that suppressor T cells would be capable of inhibiting other T cells, and thereby mediate immunological tolerance and self/non-self discrimination.
The concept of suppression mediated by T cells is nearly as old as the discovery of T cells as a separate lineage of lymphocytes. Recent reports have also demonstrated that Foxp3 + Treg cells may differentiate in vivo into conventional effector Th cells, with or without concomitant downregulation of Foxp3. Suppressive activities attributed to Treg cells may in reality, at least in some experimental settings, be exerted by conventional Th cell subsets, such as Th1, Th2, Th17 and T follicular (Tfh) cells. The classification of Treg cells as a separate lineage remains controversial because the ability to suppress is not an exclusive Treg property. It has been proposed that Treg cells would be self-reactive, but extensive TCR repertoire analysis suggests that self-reactivity may be the exception rather than the rule. Treg-cell activation is antigen-specific, which implies that suppressive activities of Treg cells are antigen-dependent. Identification of Treg cells remains problematic, because accumulating evidence suggests that all the presently-used Treg markers (CD25, CTLA-4, GITR, LAG-3, CD127 and Foxp3) represent general T-cell activation markers, rather than being truly Treg-specific. Suggested functions for Treg cells include: prevention of autoimmune diseases by maintaining self-tolerance suppression of allergy, asthma and pathogen-induced immunopathology feto-maternal tolerance and oral tolerance. This review briefly summarizes the current knowledge in the Treg field and defines some key questions that remain to be answered. Treg cells are defined as CD4 + T cells in charge of suppressing potentially deleterious activities of Th cells. Th cells control adaptive immunity against pathogens and cancer by activating other effector immune cells. CD4 + T cells are commonly divided into regulatory T (Treg) cells and conventional T helper (Th) cells.
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