Regulation of peripheral T cell activation by calreticulin

Simona Porcellini, Elisabetta Traggiai, Ursula Schenk, Denise Ferrera, Michela Matteoli, Antonio Lanzavecchia, Marek Michalak, Fabio Grassi

Research output: Contribution to journalArticle

Abstract

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. JEM

Original languageEnglish
Pages (from-to)461-471
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number2
DOIs
Publication statusPublished - Feb 20 2006

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ASJC Scopus subject areas

  • Immunology

Cite this

Porcellini, S., Traggiai, E., Schenk, U., Ferrera, D., Matteoli, M., Lanzavecchia, A., Michalak, M., & Grassi, F. (2006). Regulation of peripheral T cell activation by calreticulin. Journal of Experimental Medicine, 203(2), 461-471. https://doi.org/10.1084/jem.20051519