Clonal Anergy Is Maintained Independently of T Cell Proliferation

• DOI: 10.4049/jimmunol.169.11.6178
• Publication Date: 2014-04-20T23:41:24Z
• Authors: Sara Colombetti; Fabio Benigni; Veronica Basso; Anna Mondino
• Keywords: Clonal anergy; Clonal deletion

Abstract Ag encounter in the absence of proliferation results establishment T cell unresponsiveness, also known as clonal anergy. Anergic cells fail to proliferate upon restimulation because inability produce IL-2 and properly regulate G1 cycle checkpoint. Because optimal TCR CD28 engagement can elicit IL-2-independent progression, we investigated whether CD3/CD28-mediated activation anergic could overcome block, drive proliferation, thus reverse We show here that although antigenic stimulation fails G1-to-S transition, anti-CD3/CD28 mAbs allow proper progression cells. However, division does not restore responsiveness. Our data instead indicate reversal anergy specifically requires an IL-2-dependent, rapamycin-sensitive signal, which is delivered independently proliferation. Thus, by tracing responsiveness individual cells, whereas both TCR/CD28 IL-2-generated signals only IL-2/IL-2R interaction regulates responsiveness, indicating be regulated.