STUDIES ON THE INDUCTION AND EXPRESSION OF T CELL-MEDIATED IMMUNITY: VII. INACTIVATION OF AUTOLOGOUS CYTOTOXIC T LYMPHOCYTES WHEN USED AS BOTH EFFECTORS AND TARGETS IN A LECTIN-DEPENDENT CELLULAR CYTOTOXIC REACTIO,N

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Abstract

In vivo or in vitro generated cytotoxic thymus-derived lymphocytes (CTL) against allogeneic targets can lyse unrelated and syngeneic targets of tumor, blast, or normal cell origin in the presence of phytohemagglutinin (PHA) or concanavalin A through a lectin-dependent cellular cytotoxicity (LDCC) 51chromium release assay. In this study, several lines of evidence are presented which demonstrate that CTL inactivate and probably lyse an autologous population containing CTL in the presence of PHA through an LDCC reaction: (1) A CTL population loses its ability to mediate both specific cell-mediated cytotoxicity and nonspecific LDCC after incubation with PHA, demonstrating that CTL are rendered nonfunctional. (2) Cytotoxicity is observed when 51chromium-labeled CTL are incubated with PHA, demonstrating that CTL serve as both effectors and targets in an LDCC reaction. (3) The kinetics, as well as the lectin dose dependence of possible autologous CTL inactivation and lysis, are similar to LDCC, suggesting that they are one and the same reaction.

The possible inactivation of autologous CTL by an LDCC-mediated phenomenon is further substantiated by the following:

(1) PHA toxicity against CTL is ruled out, as isolated single cells from CTL-enriched lymphocyte populations are not killed;

(2) the kinetics of CTL inactivation argue against PHA hindrance of intercellular contact; and (3) nonlectin-mediated agglutination of CTL did not lead to a reduction in lysis.

Our results are consistent with the notion that the lethal hit stage is nonspecific and does not involve specific antigen-receptor interactions. Furthermore, our studies imply that CTL are endowed with the capacity to kill and to be killed by autologous CTL and that PHA or concanavalin A may be responsible for bringing together specialized membrane structures involved in lysis. The susceptibility of CTL to inactivation mediated by lectin, possibly provides a new mechanism for in vivo regulation of CTL and other immunocompetent cells through endogenous lectins and LDCC.

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