Superior DLI-mediated GVL effects in mixed chimeras are dependent on host MHC class I expression.

To evaluate the effect of expression of host MHC class I on hematopoietic cells on the GVL effect mediated by DLI, we established full donor chimeras (⋄, full), mixed chimeras (▿, B6+B10.A), or mixed chimeras in which host-type hematopoietic cells were deficient in host MHC class I expression (○, B6.β2m^−/−+ B10.A). Following BMT, chimeric animals received DLI with or without EL4 leukemia cells (full + DLI [∗, n = 4]; B6 + B10.A + DLI [×, n = 3]; B6.β2m^−/− + B10.A + DLI [+, n = 3]). Chimeras receiving no additional treatment after BMT were used as controls (⋄, full [n = 3]; ▿, B6 + B10.A [n = 3]; ○, B6.β2m^−/− + B10.A [n = 2]). DLI was administered on day 56 followed by EL4 leukemia administration on day 63. (A) Survival of all groups. Leukemic wild-type mixed chimeras receiving DLI demonstrated significantly longer survival (▾, 9 of 10 surviving) compared to full donor chimeras (♦, 0 of 9 surviving MST 91 days). Leukemic B6.β2m^−/− + B10.A chimeras revealed an intermediate result (●, 4 of 7 animals surviving). (B) Survival analysis in leukemic B6.β2m^−/− + B10.A chimeras stratified according to peripheral blood chimerism levels in the monocytic lineage. Animals with high (▪, more than 40% B6.β2m^−/− monocytes) or low (■) B6.β2m^−/− hematopoiesis receiving DLI+EL4 are compared to wild-type B6 + B10.A chimeras receiving DLI + EL4 (▾). Full chimeras receiving DLI + EL4 (♦) are also shown for comparison. B6.β2m^−/− + B10.A mixed chimeras with low B6.β2m^−/− hematopoiesis receiving DLI and EL4 showed a significantly poorer survival than animals with high levels of B6.β2m^−/− hematopoiesis (P < .0002).