Impaired Ca/calcineurin pathway in in vivo anergized CD4 T cells

Clonal anergy is one of the mechanisms that may account for self tolerance induced in T cells in the periphery. In this study we used the well-documen ted system of in vivo administration of a superantigen, staphylococcal ente rotoxin B (SEB), to induce a stale of hyporesponsiveness (anergy) in murine peripheral T cells to decipher the intracellular biochemical basis for thi s process. The TCR-induced Ca response of in vitro activated T cells was fo und to be impaired with significant defects in the phosphorylation of phosp holipase C-gamma 1. Experiments with calcium ionophore and newly establishe d transgenic mouse lines that express an active form of calcineurin suggest ed that in vivo SEE-induced anergy is established and/or maintained by a se lective impairment in the TCR-induced activation of the Ca/calcineurin path way.