Target cell-induced inactivation of cytolytic lymphocytes. Role and regulation of CD45 and calyculin A-inhibited phosphatase in response to interleukin-2.
Cytolytic T lymphocyte (CTL) and natural killer cells (NK) lose their lytic potential after interaction with sensitive target cells that can be restored upon incubation with interleukin-2. In this study we observed that preincubation with Ser/Thr phosphatase inhibitor calyculin A inhibited both CTL and NK cell-mediated cytotoxicity (CMC) in a dose-dependent manner. In contrast, okadaic acid inhibited only CTL-CMC without significantly affecting NK-CMC. Incubation of CTL and NK cells with their sensitive TC inhibited both CTL-CMC by 74% and NK-CMC by > 80%. This loss in lytic activity was accompanied by a loss of 60% and > 80% in the cellular p-nitrophenyl phosphate phosphatase (pNPPase) activity in CTL and NK cells, respectively. When treated with 100 units/ml interleukin-2 for 16-18 h at 37 degrees C, inactivated CTL and NK cells recovered 70% and 100% of their lytic activity and approximately 60% and 100% of phosphatase activity, respectively. Analysis revealed that > 80% of the pNPPase activity was associated with membrane-bound CD45, and it is this phosphatase activity that was reversibly affected by target cell-induced inactivation/reactivation of CTL and NK cells. These results suggest that Ser/Thr phosphatases and CD45 play a key role in modulating the lytic activity of effector cells exposed to sensitive target cells.
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
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Bajpai
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Brahmi
D000328:Adult; D002451:Cell Compartmentation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007376:Interleukin-2; D008387:Marine Toxins; D010080:Oxazoles; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens