INDUCTION OF INCREASED GRAFT-VERSUS-HOST DISEASE BY MOUSE SPLEEN CELLS SENSITIZED IN VITRO TO ALLOGENEIC TUMOR

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Abstract
The aim of this study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-vs.-host disease (GVHD). C57BL/6 (H-2b) spleen cells were incubated with irradiated BALB/c (H-2d) Moloney lymphoma cells (LSTRA) in mixed leukocyte culture conditions for 2, 4 or 6 days and then tested. The maximal proliferative response occurred after 4 days. In vitro cytotoxic reactivity against 51Cr-labeled LSTRA was generated by 4 days (76.3 .+-. 3.1% 51Cr released) and 6 days (133.0 .+-. 4.8%) of sensitization but not by 2 days (-0.2 .+-. 1.1%). Induction of fatal GVHD was assayed by injecting graded doses of the C57BL/6 spleen cells i.v. into adult BALB/c mice pretreated with cyclophosphamide, 180 mg/kg. Cells sensitized for 2 days were effective but no more so than were (control) cells cultured with irradiated C57BL/6 spleen cells. Cells sensitized longer were far more active than the control cells. Cells sensitized for 4 days killed 70 of 88 mice (80%), and those sensitized for 6 days killed 37 of 48 mice (77%), whereas control cells killed only 42 of 90 mice (47%) (P < 0.005). Thus, cells sensitized in vitro exhibited an increased ability to induce GVHD in vivo, which was temporally associated with the development of cytotoxicity in vitro.

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