V. Schirrmacher et al., GENETIC SEPARATION OF GVL AND GVH REACTIVITY IN NEW RECOMBINANT-INBRED TUMOR-RESISTANT MOUSE STRAINS, International journal of oncology, 8(6), 1996, pp. 1035-1043
From a cross between a tumor-susceptible syngeneic mouse strain (DBA/2
) and a tumor resistant MHC congenic strain (B10.D2) new recombinant i
nbred mouse strains were established over many generations of inbreedi
ng 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. Sin
ce tumor resistance had an immunological basis and since the two paren
tal 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 a
lso tested the capacity of immune cells from 7 resistant lines to tran
sfer graft versus leukemia and graft versus host reactivity to ESb tum
or bearing DBA/2 mice. Immune cells from one subline were capable of t
ransfering 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.