| Abstrakt: |
The aim of our study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-versus-host disease (GVHD). C57BL/6 (H2b) spleen cells were incubated with irradiated BALB/C (H2d) 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 \pm 3.1 51Cr released) and 6 days (133.0 \pm 4.8) of sensitization but not by 2 days (-0.2 \pm 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. However, 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. |
