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RESEARCH PRODUCT

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

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SUMMARY The 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.