EFFECT OF M‐LOCUS DEPENDENT T‐CELL PROLIFERATION UPON THE INDUCTION OF ANTI H‐2 CYTOTOXIC T EFFECTOR CELLS

Abstract

SUMMARYThe influence of M‐locus dependent T cell proliferation on the induction of anti H‐2 cytotoxic T lymphocytes (CTL) was tested in an in vitro murine cytotoxic allograft model. BALB/c (or CBA/H) derived responder cells (H‐2d or H‐2k) were cultured together with either C57BL derived fibroblasts or C57BL derived (H‐2b), U.V. light irradiated, splenic lymphocytes. These stimulator cells lack functionally active lymphocyte activating determinants (LADs), but display serologically defined (SD) H‐2 antigenic specificities. The cytotoxic anti SD‐activity obtained was weak. Under certain experimental conditions, the addition of stimulator cells which are H‐2 identical to the responder cells but differ at the M‐locus (either DBA/2 or AKR strain derived) gave an enhanced cytotoxic anti SD H‐2 specificity directed activity (three cell experiments)—findings in keeping with the ‘two signal’ hypothesis for the production of CTL during in vitro alloimmune interaction: they also suggest that LADs encoded by the M‐locus can, under these circumstances, substitute for MHC I region incompatibility. However, in some experiments, in which M‐locus different third party cells were added to normal one way mixed lymphocyte cultures, a suppressive effect could be observed upon the generation of CTL. Furthermore, 2‐mercaptoethanol together with M‐locus incompatible cells regularly suppressed, rather than amplified, the production of CTL. The addition of mercaptoethanol alone without M‐locus incompatible cells had an amplifying effect on the production of CTL when fibroblast stimulators were used. The roles of M‐locus LADs and mercaptoethanol are clearly complex and require further investigations.