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CD38 is functionally dependent on the TCR/CD3 complex in human T cells
Author(s) -
Morra Massimo,
Zubiaur Mercedes,
Terhorst Cox,
Sancho Jaime,
Malavasi Fabio
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.7.581
Subject(s) - jurkat cells , cd3 , t cell receptor , microbiology and biotechnology , cd38 , cd28 , t cell , signal transduction , cytoplasm , phosphorylation , biology , chemistry , cd8 , immunology , immune system , stem cell , cd34
One of the functions of surface CD38 is the induction of phosphorylation of discrete cytoplasmic substrates and mobilization of cytoplasmic calcium (Ca 2+ ). The present work addresses the issue of whether the signaling mediated via CD38 operates through an independent pathway or, alternatively, is linked to the TCR/CD3 signaling machinery. We studied the signals elicited through CD38 by the specific agonistic IB4 monoclonal antibody (mAb) by monitoring the levels of cytoplasmic Ca 2+ and the induced phenotypic and functional variations in T cell growth. IB4 mAb presented the unique ability to increase cytoplasmic Ca 2+ levels, which correlated with the phosphorylation of the PLC‐γ1. These effects were blocked by phorbol 12‐myristate 13‐acetate (PMA) and were dependent on the presence of a functional TCR/CD3 surface complex, no effects being recorded on mutant Jurkat cells lacking part of the CD3 structures. CD38 signaling appeared to share with TCR/CD3 the ability to induce apoptotic cell death in Jurkat T cells, an event paralleled by specific up‐regulation of the Fas molecule and inhibited by cyclosporin A. CD28, a costimulatory molecule, is synergized by increasing CD38‐induced apoptotic cell death. The results indicate the existence of a strong functional interdependence between CD38 and TCR/CD3.