Graft-versus-leukemia reactivity involves cluster formation between superantigen-reactive donor T lymphocytes and host macrophages

T-cell-mediated antitumor effects play an important role clinically in allo geneic graft-versus-leukemia (GvL) reactivity, whereas T-cell-mediated anti host effects are associated with a risk of developing graft-versus-host (GV H) disease. GvL and GvH were compared;in an animal tumor model system after the systemic transfer of allogeneic antitumor immune T lymphocytes from B1 0.D2 [H-2(d); minor lymphocyte-stimulating antigen (Mls) (b)] mice into ESb -MP tumor-bearing or normal DBA/2 (H-2(d); Mls(a)) mice. Here we demonstrat e that this T-cell-mediated therapy involves the formation of clusters of d onor CD4 and CDS T cells with host macrophages, in particular, with a subpo pulation expressing the lymphocyte adhesion molecule sialoadhesin. DBA/2 mi ce and the derived tumor ESb-MP express viral superantigen 7 (Mls(a)), an e ndogenous viral superantigen that is absent from B10.D2 mice. To test the c ontribution of viral superantigen 7-reactive V beta 6 donor T cells in the GvL-mediated eradication of liver metastases, we performed immunohistologic al and transmission electron microscopy studies. V beta 6+ CD4 and CD8 T ce lls from B10.D2 donors formed tight clusters with host sialoadhesin-positiv e macrophages, and transmission electron microscopy pictures revealed direc t membrane-membrane interactions between T cells and macrophages, Clusters were more abundant and consisted of more cells in tumor-bearing hosts (GvL model) than in non-tumor-bearing hosts (GvH model), In addition, V beta 6 T cells within the clusters showed a strong proliferation activity, indicati ng stimulation. Moreover, in an in vitro tumor cytostasis assay, primed as well as nonprimed purified V beta 6 T cells from donor mice were able to in hibit the proliferation of superantigen-expressing ESb-MP lymphoma cells. T his suggests that the transferred superantigen-reactive V beta 6 T cells co ntribute to the eradication of metastases, The observed cell dusters might be sites for antigen presentation and the activation of tumor-reactive T ce lls.