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

✍ Scribed by Mirjana Lilić; Kimary Kulig; Ilhem Messaoudi; Kristin Remus; Mila Janković; Janko Nikolić-Žugić; Stanislav Vukmanović

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 156 KB
• Volume: 29
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(199912)29:12<3971::aid-immu3971>3.0.co;2-5

✦ Synopsis

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.