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Letters to Nature
Nature 384, 263 - 266 (21 November 1996); doi:10.1038/384263a0

Alternative pathways for the selection of antigen-specific peripheral T cells

Biao Zheng, Shuhua Han, Qing Zhu, Richard Goldsby* & Garnett Kelsoe

Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Maryland 21201, USA
*Department of Biology, Amherst College, Amherst, Massachusetts 01002, USA

IN the thymus, maturing lymphocytes receive activation signals mediated by the T-cell antigen receptor (TCR) that either promote clonal survival (positive selection) or induce apoptosis (negative selection). This balance between life and death is mirrored by the sensitivity of cortical thymocytes to apoptotic death induced by antibodies against the CD3 component of the TCR signal-transduction complex, bacterial superantigens that bind to the TCR β-chain, and corticosteroids1,3. In contrast, mature peripheral T cells are positively activated by anti-CD3 antibody or superantigens and are resistant to steroid-induced death4,5. Here we show that in splenic germinal centres, T cells regain thymocyte-like sensitivity to TCR- and steroid-induced apoptosis and undergo antigen-driven positive and negative selection. T-cell responses elsewhere in the spleen are unaccompanied by programmed cell death. Our observations define a new differentiation pathway for peripheral T cells and suggest that germinal centres induce a lymphocyte phenotype necessary for the maintenance of self-tolerance.

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