Cytotoxic T lymphocyte (CTL)-mediated cytolysis proceeds in the absence of Na+/H+ antiport activity: regulation of cytosolic pH by the Na+/H+ antiport in a cloned CTL.
Cytotoxic T lymphocyte (CTL)-mediated cytolysis of specifically bound target cells (TC) is thought to be triggered by cross-linking the T-cell antigen receptor (TcR). Biochemical events associated with TcR cross-linking include increased intracellular calcium levels [Ca2+]i, hydrolysis of phosphatidylinositol (PI), and an increase in intracellular pH [pH]i. Whereas CTL-mediated cytolysis of some TC is calcium-dependent, and PI hydrolysis is speculated to trigger the CTL lethal hit via activation of PKC, little is known about changes in [pH]i relating to activation of the lethal hit stage. We report regulation of [pH]i in a cloned CTL by the electroneutral Na+/H+ antiport during activation with PMA and specific antigen-bearing TC. Furthermore, using 5-(N-methyl-N-isobutyl) amiloride (MIBA), a potent antiport inhibitor, we demonstrate that Na+/H+ exchange is not required for activation of CTL cytolytic activity.
Howcroft
T K
TK
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Loew
L M
LM
Cragoe
E J
EJ
Lindquist
R R
RR
D000136:Acid-Base Equilibrium; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008985:Monensin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D008985:Monensin; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate