Genetic separation of GvL and GvH reactivity in new recombinant-inbred tumor-resistant mouse strains

Abstract

From a cross between a tumor-susceptible syngeneic mouse strain (DBA/2) and a tumor resistant MHC congenic strain (B10.D2) new recombinant inbred mouse strains were established over many generations of inbreeding and tumor resistance selection. The resistance selected against one DBA/2 derived malignant tumor (ESb) extended to other DBA/2 malignant tumors (SL 2, MDAY-D2) and was thus of more general significance. Since tumor resistance had an immunological basis and since the two parental strains differed in multiple minor histocompatibility antigens (H) as well as in viral superantigens (vSAGs) we determined specificities of cytotoxic T lymphocyte (CTL) responses in vitro. All CTL responses from tumor resistant strains showed not only antitumor reactivity but also rather strong anti-minor H reactivity. There was no relationship between cytolysis and the DBA/2 type vSAG-7 (Mls(a)) expression. We also tested the capacity of immune cells from 7 resistant lines to transfer graft versus leukemia and graft versus host reactivity to ESb tumor bearing DBA/2 mice. Immune cells from one subline were capable of transfering complete protection without development of chronic GVH over a period of 4 months. The resistant parental line B10.D2 and most of the other sublines also were able to transfer GvL reactivity but this was usually associated later with chronic GVH disease caused mortality. These results demonstrate the potential of this genetic approach to separate GvL from GvH reactivity.