| First Author | Porcellini S | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 2 | Pages | 461-71 |
| PubMed ID | 16492806 | Mgi Jnum | J:119147 |
| Mgi Id | MGI:3701376 | Doi | 10.1084/jem.20051519 |
| Citation | Porcellini S, et al. (2006) Regulation of peripheral T cell activation by calreticulin. J Exp Med 203(2):461-71 |
| abstractText | Regulated expression of positive and negative regulatory factors controls the extent and duration of T cell adaptive immune response preserving the organism's integrity. Calreticulin (CRT) is a major Ca2+ buffering chaperone in the lumen of the endoplasmic reticulum. Here we investigated the impact of CRT deficiency on T cell function in immunodeficient mice reconstituted with fetal liver crt-/- hemopoietic progenitors. These chimeric mice displayed severe immunopathological traits, which correlated with a lower threshold of T cell receptor (TCR) activation and exaggerated peripheral T cell response to antigen with enhanced secretion of inflammatory cytokines. In crt-/- T cells TCR stimulation induced pulsatile cytosolic elevations of Ca2+ concentration and protracted accumulation of nuclear factor of activated T cells in the nucleus as well as sustained activation of the mitogen-activated protein kinase pathways. These observations support the hypothesis that CRT-dependent shaping of Ca2+ signaling critically contributes to the modulation of the T cell adaptive immune response. |
