Effect of graft-versus-host disease on anti-tumor immunity

BCL₁, a spontaneous B cell leukemia of BALB/c origin, is rejected by C.B-20 (Igh^b, H-40^b) but not BALB/c (Igh^a, H-40^a) mice. Adoptive transfer of C.B-20 anti-BCL₁ effector cells specific for the minor histocompatibility Ag H-40a protects irradiated C.B-20 but not BALB/c recipients. Because C.B-20 donor cells could potentially generate graft-vs-host disease (GVHD) in BALB/c recipients, we investigated the possibility that GVHD prevents the anti-tumor effect. GVHD was induced in (C.B-20 × B10.D2)F₁ [H-2^d, H-40^b,× H-2^d, H-40^b] recipients after injection of B10.D2-primed C.B-20 donor cells. GVHD was indicated by the histologie appearance of tissue sections from C.B-20→F₁ livers, target organs of GVHD, which showed a marked mononuclear cell infiltrate around the portal tracts and central veins. In addition, splenic lymphocytes from these mice had altered CD4/CD8 ratios and were unable to respond to the polyclonal activators Con A and LPS. The mitogen unresponsiveness was at least partially due to the presence of a suppressor cell, because proliferation of normal spleen cells to Con A and LPS was suppressed upon addition of C.B-20→F₁ spleen cells. Further immune dysfunction was evident by the inability of T cells from mice with GVHD to generate a CTL response to H-2 alloantigens. Addition of C.B-20-→F₁ spleen cells to F₁ responder cells at the induction of culture did not prevent generation of CTL, indicating that a suppressor cell was not responsible for the lack of CTL activity. In this setting of GVHD, F₁ recipients were able to reject BCL₁ upon adoptive transfer of C.B-20 anti-BCL₁ effector cells. These data indicate that GVHD-induced immune dysfunction does not inhibit the activity of antileukemia T cells.