Radiosensitivity and responsiveness to recombinant interleukin-2 of effector cells of graft vs. host disease and mixed lymphocyte reaction in mice.
Synergistic effects of recombinant interleukin-2 (IL-2) or irradiated spleen cells were investigated in vivo and in vitro. Irradiated (750 cGy) C57BL/6 spleen cells infused to sublethally irradiated (500 cGy) BALB/c mice treated with IL-2 (1,000 U 3 times/day) caused graft vs. host-like disease (GVHD) in 3 of 11 mice. Similarly irradiated allogenic spleen cells caused no GVHD in irradiated recipients not administered IL-2. No sign of autologous GVHD was found in mice that received irradiated syngeneic spleen cells with IL-2. Addition of recombinant IL-2 in vitro to mixed lymphocyte reactions (MLR) using irradiated (500 cGy) allogeneic responder spleen cells augmented the 3H-TdR uptake fourfold compared to cultures without IL-2, but was 44-fold below the allogeneic response of nonirradiated C57BL/6 spleen cells. Il-2-induced cell proliferation was also noted in syngeneic MLR, but did not lead to GVHD in in vivo experiments. The data suggest that IL-2 may potentiate GVHD and alloreactivity induced by an adequate number of irradiated, nondividing but viable allogeneic spleen cells and/or that secretion of IL-2 by alloactivated T lymphocytes, supplied exogenously in the present study, may play a role in the GVHD syndrome. Since neither viable but nonreplicating T cells nor IL-2 alone caused GVHD, it is suggested that endogenously produced IL-2 by alloactivated T lymphocytes may be important in the development of the GVHD syndrome, independent of its main function of enhancing T lymphocyte proliferation. On the other hand, the lack of GVHD following administration of high numbers of irradiated or nonirradiated syngeneic spleen cells with IL-2 implies that allogeneic T lymphocytes and not IL-2 activated MHC-nonrestricted cytotoxic cells play a role in inducing the GVHD syndrome in vivo.
Stark
J
J
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Weiss
L
L
Slavin
S
S
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000528:radiation effects* / Q000637:transplantation
D007376:Interleukin-2; D011994:Recombinant Proteins