Memory-Like CD8 and CD4 T Cells Cooperate to Break Peripheral
Memory-like CD8؉ and CD4؉ T cells cooperate to break peripheral tolerance under lymphopenic conditions Cecile Le Saout, Sandie Mennechet, Naomi Taylor, and Javier Hernandez1 Institut de Ge´ne´ tique Mole´culaire de Montpellier Unite´Mixte de Recherche 5535, Centre National de la Recherche Scientifique, Université de Montpellier 1 and 2, 34293 Montpellier, Cedex 5, France Edited by N. Avrion Mitchison, University College London, London, United Kingdom, and approved October 20, 2008 (received for review August 10, 2008) The onset of autoimmunity in experimental rodent models and established (9). In the case of naive T cells, T cell antigen receptor patients frequently correlates with a lymphopenic state. In this (TCR) interactions with MHC/self-peptide complexes (those that condition, the immune system has evolved compensatory homeo- mediate positive selection) and the IL-7 cytokine appear to be static mechanisms that induce quiescent naive T cells to proliferate required for this expansion (10–15). Recently, an IL-7 independent and differentiate into memory-like lymphocytes even in the apparent form of lymphopenia-driven proliferation has also been described absence of antigenic stimulation. Because memory T cells have less (16). However, in all these cases, proliferating cells differentiate and stringent requirements for activation than naive cells, we hypothe- acquire a memory-like phenotype and the ability to rapidly secrete sized that autoreactive T cells that arrive to secondary lymphoid effector cytokines (12, 17–19). Although memory-like T cells have organs in a lymphopenic environment could differentiate and bypass never been activated by cognate antigen, do not pass through an the mechanisms of peripheral tolerance such as those mediated by effector phase, and, as such, cannot be considered to be ‘‘true’’ self-antigen cross-presentation.
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