ALTERNATIVE PATHWAYS FOR THE SELECTION OF ANTIGEN-SPECIFIC PERIPHERALT-CELLS

IN the thymus, maturing lymphocytes receive activation signals mediate d by the T-cell antigen receptor (TCR) that either promote clonal surv ival (positive selection) or induce apoptosis (negative selection), Th is balance between life and death is mirrored by the sensitivity of co rtical thymocytes to apoptotic death induced by antibodies against the CD3 component of the TCR signal-transduction complex, bacterial super antigens that bind to the TCR beta-chain, and corticosteroids(1-3). In contrast, mature peripheral T cells are positively activated by anti- CD3 antibody or superantigens and are resistant to steroid-induced dea th(4,5). 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 respons es 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 phenotyp e necessary for the maintenance of self-tolerance.