Peripheral Clonal Elimination of Functional T Cells

Abstract

A major mechanism for generating tolerance in developing T cells is the intrathymic clonal deletion of T cells that have receptors for those self antigens that are presented on hematopoietic cells. The mechanisms of tolerance induction to antigens not expressed in the thymus remain unclear. Tolerance to self antigens can be generated extrathymically through the induction of clonal nonresponsiveness in T cells with self-reactive receptors. A second mechanism of extrathymic tolerance was identified: clonal elimination of mature T cells with self-reactive receptors that had previously displayed functional reactivity.

Kinetics and Repertoire Selection of T Cells Derived from the Early Waves of Fetal Thymus Colonization After Thymus Grafting in Allogeneic Nude Recipients

“…The lower representation of Vb5 and Vb11 among donor T cells later on suggests that peripheral deletion might occur in our chimeras, as previously shown [26], possibly by additional antigen encounter on peripheral cells [27]. On the other hand, variability in Vb representation, usually important within chimeras [23], might also account for the lower Vb representation observed.…”

Identification and quantitation of apoptotic cells following anti‐CD3 activation of murine G0 T cells

“…DNA from each of the sorted cell populations was isolated and subjected to DNA gel electrophoresis. The results of gel electrophoresis shown in Figure 2, lanes (6)(7)(8), (Fig. lC), whereas HO-High cells (R2) clustered as high FSC-low SSC events (Fig.…”

“…It is well known that anti-CD3 antibodies can induce apoptotic cell death in thymocytes (5, 11,12,17), in T-cell hybridomas (6,14,20), and in established T-cell lines (9,21). Although the response of mature T cells to anti-CD3 antibodies typically results in T-cell proliferation (l), some recent studies have demonstrated that mature T cells undergo apoptosis and clonal deletion in response to TCRaIP and TCRP antibodies (7,131. The ability of anti-CD3 to induce some T cells to proliferate while triggering programmed cell death in others remains the subject of intense investigation.…”

Organ injury associated with extrathymic induction of immune tolerance in doubly transgenic mice.

“…4). At birth (5,6,9,11,(19)(20)(21)(22)(23)(24). Likewise, EL singly transgenic mice did not develop spontaneous autoimmunity in exocrine pan- creas.…”