The Journal of Immunology, Vol 149, Issue 4 1265-1270, Copyright © 1992 by American Association of Immunologists

ARTICLES

Differences between ATP-mediated cytotoxicity and cell-mediated cytotoxicity

RK Avery, KJ Bleier and MS Pasternack
Infectious Disease Unit Children's and Medical Services, Massachusetts General Hospital, Boston 02114.

There has been considerable recent interest in the possible role of extracellular ATP in cell-mediated cytotoxicity. To investigate the similarities and differences between ATP-mediated lysis and CTL- mediated lysis, we studied in detail the ATP-mediated lysis of EL-4 cells, which are highly susceptible to lysis by extracellular ATP. ATP- mediated lysis was time and concentration dependent; most lysis occurred within 4 to 6 h of incubation. The kinetics of ATP- and cell- mediated lysis were similar. However, in contrast to CTL-mediated lysis, ATP-mediated lysis of EL-4 cells did not appear to be accompanied by characteristic chromosomal degradation (apoptosis). In order to compare these cytotoxic processes in greater detail, ATP- resistant clones were derived by growing EL-4 cells continuously in the presence of high concentrations of ATP. These cloned EL-4 lines showed marked resistance to ATP-mediated cytotoxicity across a wide range of concentrations but were as susceptible as the parent EL-4 cells to cell- mediated cytotoxicity by an alloreactive effector population from a MLC. Thus, there appear to be a number of differences between ATP- mediated and cell-mediated cytotoxicity in this system; most notable is the identification of cell lines that are resistant to ATP but susceptible to CTL-mediated lysis.

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