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

Cytotoxicity is a major effector function of CD8(+) T cells. Although mitog en-activated protein kinase (MAP kinase)/extracellular regulatory kinase (E RK) activity is indispensable for cytotoxic activity of most CD8(+) T cells a portion of CD8(+) T cells appears resistant to MEK inhibition as cytotox icity of bulk cultures was partially preserved in the presence of a MEK inh ibitor. We have also identified a long-term CD8(+) T cell line with unalter ed cytolytic activity after prevention of ERK activation. Antigen-induced m icrotubule organizing center (MTOC) reorientation was not prevented in this CD8(+) cell line by MEK inhibition, in sharp contrast to the MTOC reorient ation prevention in a CD8(+) T cell clone with MEK inhibition-sensitive cyt olytic activity. These findings suggest that resistance of lysis to MEK inh ibition 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 differe ntial control of ERK over MTOC motility.