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-documented system of in vivo administration of a superantigen, staphylococcal enterotoxin B (SEB), to induce a state of hyporesponsiveness (anergy) in murine peripheral T cells to decipher the intracellular biochemical basis for this process. The TCR-induced Ca response of in vitro activated T cells was found to be impaired with significant defects in the phosphorylation of phospholipase C-gamma 1. Experiments with calcium ionophore and newly established transgenic mouse lines that express an active form of calcineurin suggested that in vivo SEB-induced anergy is established and/or maintained by a selective impairment in the TCR-induced activation of the Ca/calcineurin pathway.
Kimura
M
M
Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
Yamashita
M
M
Kubo
M
M
Iwashima
M
M
Shimizu
C
C
Tokoyoda
K
K
Chiba
J
J
Taniguchi
M
M
Katsumata
M
M
Nakayama
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*
D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal; D019703:Calcineurin; D002118:Calcium