CD8+ T cell cytolytic activity independent of mitogen-activated protein kinase/extracellular regulatory kinase signaling (MAP kinase/ERK)

Mirjana Lilić, Kimary Kulig, Ilhem Messaoudi, Kristin Remus, Mila Janković, Janko Nikolić-Žugić, Stanislav Vukmanović

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3971-3977
Number of pages7
JournalEuropean Journal of Immunology
Volume29
Issue number12
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • CTL
  • Cytolysis
  • ERK
  • MAP kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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