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CD8 + T cell cytolytic activity independent of mitogen‐activated protein kinase / extracellular regulatory kinase signaling (MAP kinase / ERK)
Author(s) -
Lilić Mirjana,
Kulig Kimary,
Messaoudi Ilhem,
Remus Kristin,
Janković Mila,
NikolićŽugić Janko,
Vukmanović Stanislav
Publication year - 1999
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/(sici)1521-4141(199912)29:12<3971::aid-immu3971>3.0.co;2-5
Subject(s) - mapk/erk pathway , biology , microbiology and biotechnology , cytolysis , cytotoxic t cell , protein kinase a , kinase , in vitro , biochemistry
Abstract Cytotoxicity is a major effector function of CD8 + T cells. Although mitogen‐activated protein kinase (MAP kinase) / extracellular regulatory kinase (ERK) activity is indispensable for cytotoxic activity of most CD8 + T cells a portion of CD8 + T cells appears resistant to MEK inhibition as cytotoxicity of bulk cultures was partially preserved in the presence of a MEK inhibitor. We have also identified a long‐term CD8 + T cell line with unaltered cytolytic activity after prevention of ERK activation. Antigen‐induced microtubule organizing center (MTOC) reorientation was not prevented in this CD8 + cell line by MEK inhibition, in sharp contrast to the MTOC reorientation prevention in a CD8 + T cell clone with MEK inhibition‐sensitive cytolytic activity. These findings suggest that resistance of lysis to MEK inhibition may be due to a lack of ERK control over MTOC reorientation in some CD8 + T cells. Thus, there appears to be a heterogeneity of ERK‐regulated cytolytic activity in CD8 + T cells, most likely resulting from a differential control of ERK over MTOC motility.