DIFFERENCES BETWEEN GRAFT-VERSUS-LEUKEMIA AND GRAFT-VERSUS-HOST REACTIVITY .1. INTERACTION OF DONOR IMMUNE T-CELLS WITH TUMOR AND OR HOST-CELLS/

Graft-versus-leukemia (GVL) and Graft-versus-host (GVH) reactions were compared after systemic transfer of allogeneic antitumor immune T lym phocytes from B10.D2 (H-2(d); Mls(b)) into DBA/2 (H-2(d); Mls(8)) mice . Before immune cell transfer, recipient DBA/2 mice were sublethally i rradiated with 5 G gamma to prevent host-versus-graft reactivity. Reci pients were either bearing syngeneic metastatic ESb lymphomas (GVL sys tem) or were normal, non-tumor-bearing mice (GVH system). We previousl y reported that this adoptive immunotherapy protocol (ADI) had pronoun ced GVL activity and led to immune rejection of even advanced metastas ized cancer. In this study, monoclonal antibodies were used for immuno histochemical analysis of native frozen tissue sections from either sp leen or liver to distinguish donor from host cells, to differentiate b etween CD4 and CD8 T lymphocytes, and to stain sialoadhesin-positive m acrophages at different time points after cell transfer, The kinetics of donor cell infiltration in spleen and liver differed in that the ly mphoid organ was infiltrated earlier (days 1 to 5 after transfer) than the nonlymphoid organ (days 5 to 20), After reaching a peak, donor ce ll infiltration decreased gradually and was not detectable in the sple en after day 20 and in the liver after day 30. The organ-infiltrating donor immune cells were mostly T lymphocytes and stained positive for CD4 or CD8 T-cell markers. A remarkable GVL-associated observation was made with regard to a subset of macrophages bearing the adhesion mole cule sialoadhesin (SER(+) macrophages), In the livers of tumor-bearing mice, their numbers increased between days 1 and 12 after ADI by a fa ctor greater than 30. Double-staining for donor cell marker and SER sh owed that the sialoadhesin-expressing macrophages were of host origin. The SER(+) host macrophages from GVL livers were isolated by enzyme p erfusion and resetting 12 days after ADI, when they reached peak value s of about 60 cells per liver lobule, and were tested, without further antigen addition, for their capacity to stimulate an antitumor CD8 T- cell response. The results of this immunologic analysis suggest that t hese cells in the liver function as scavengers of the destroyed metast ases and as antigen-processing and -presenting cells for antitumor imm une T cells. (C) 1997 by The American Society of Hematology.