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The Bcl‐2 family pro‐apoptotic molecule, BNIP3 regulates activation‐induced cell death of effector cytotoxic T lymphocytes
Author(s) -
Wan J.,
Martinvalet D.,
Ji X.,
Lois C.,
Kaech S. M.,
Von Andrian U. H.,
Lieberman J.,
Ahmed R.,
Manjunath N.
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01710.x
Subject(s) - ctl* , cytotoxic t cell , microbiology and biotechnology , programmed cell death , effector , biology , apoptosis , t cell , caspase , immunology , biochemistry , immune system , in vitro
Summary BNIP3 is a recently described pro‐apoptotic member of the Bcl‐2 family and in BNIP3 cDNA‐transfected cell lines, cell death occurs via a caspase‐independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Δψ m ). However, its expression or function in physiologic cell types is not known. Our results using the T‐cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl‐2 family pro‐apoptotic molecules, BNIP3 is transcriptionally highly up‐regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation‐induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3‐induced cell death. AICD of CTL was caspase‐independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3‐induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Δψ m . Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T‐cell homeostasis by regulating effector CTL numbers.