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Actually, such features are shared only by a fraction of \u03b3\u03b4 T\u2010cell subsets located in the skin and reproductive organ mucosa in rodents or in peripheral blood in humans. By contrast, other \u03b3\u03b4 subsets, e.g. those found in rodent and human spleen, show diverse antigenic reactivity patterns and mixed naive\/memory phenotypes. Thus, \u03b3\u03b4 T cells are made of both \u2018primitive\u2019 subsets endowed with innate\u2010like properties and \u2018evolved\u2019 subsets able to mount anamnestic responses like conventional major histocompatibility complex\u2010restricted \u03b1\u03b2 T cells. In this article, we show that human \u03b3\u03b4 T cells, although heterogeneous, do share recurrent innate features that distinguish them from mainstream \u03b1\u03b2 T cells. In particular, most of them are activated on TCR\u2010 or natural killer receptor\u2010mediated recognition of a restricted set of conserved yet poorly defined endogenous stress determinants. This rather simple recognition mechanism allows human \u03b3\u03b4 T cells to discriminate healthy cells from altered cells and to exert a variety of immunostimulatory or regulatory functions. The recent availability of synthetic \u03b3\u03b4 T\u2010cell agonists mimicking these natural stress\u2010induced ligands have fostered development of immunotherapeutic strategies, with broad indications against infectious and tumor diseases, which are briefly reviewed here.<\/jats:p>","DOI":"10.1111\/j.1600-065x.2006.00468.x","type":"journal-article","created":{"date-parts":[[2007,2,3]],"date-time":"2007-02-03T07:31:00Z","timestamp":1170487860000},"page":"123-135","source":"Crossref","is-referenced-by-count":119,"title":["Self\/non\u2010self discrimination by human \u03b3\u03b4 T cells: simple solutions for a complex 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