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Essential role for the beta3 regulatory subunit of L‐type calcium channel in the survival and functions of CD8 T cells
Author(s) -
Jha Mithilesh Kumar,
Badou Abdallah,
Flockerzi Veit,
Freichel Marc,
Flavell Richard
Publication year - 2008
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.22.1_supplement.661.16
Subject(s) - cytotoxic t cell , microbiology and biotechnology , cd8 , biology , calcium channel , cd28 , interleukin 21 , nfat , calcium , immunology , antigen , chemistry , in vitro , biochemistry , transcription factor , organic chemistry , gene
Peripheral survival and homeostasis of naive T lymphocytes require sustained calcium influx mediated by interaction of naive T lymphocytes with dendritic cells in the absence of cognate antigen. The molecular mechanism which governs calcium influx in naive T lymphocytes is not well understood. Here we report a critical role of beta3‐Cav1.4 calcium channel complex in regulating the calcium influx in naive CD8 T lymphocytes. Beta3 and pore forming alpha subunit of Cav1.4 calcium channel are expressed in naive CD8 T cells. Beta3 KO naive CD8 T cells did not accumulate in vivo since these cells were susceptible to apoptosis due to increased Fas expression. TCR‐mediated global calcium entry and NFAT activation were reduced in beta3 KO naive CD8 T cells. IFN‐gamma, IL‐2 and TNF‐alpha production were significantly impaired in beta3KO CD8 cells challenged with BMDCs loaded with MHC class I‐specific ovalbumin peptide. Beta3 deficiency abrogated the pore forming Cav1.4 synthesis suggesting that it regulates the functional expression of Cav1.4 subunit in naive CD8 T cells. Our data demonstrate a critical role of Cav1.4‐beta3 channel complex in regulating the calcium entry required for the survival and functions of CD8 T cells.