Effect of granulocyte-macrophage colony-stimulating factor on the induction of unresponsiveness by lymphoid cells.
Skin grafts can be significantly prolonged in ALS-treated mice by the injection of 25 x 10(6) donor bone marrow cells or 50 x 10(6) spleen cells. Lymph node cells and thymocytes are only minimally effective in prolonging grafts. The effect of a hematopoietic growth factor, granulocyte-macrophage colony stimulating factor (GM-CSF) was studied in this model of unresponsiveness. C3H/He lymphoid cell donors were treated with GM-CSF. Either normal or GM-CSF-treated cells were injected into ALS-treated B6AF1 mice grafted with C3H/He skin. GM-CSF treatment significantly augmented the effect of marrow in prolonging graft survival at doses of 1 to 25 x 10(6) cells. In contrast, GM-CSF had no effect on the graft-prolonging effect of spleen cells when 50 x 10(6) cells were given. When the dose of cells was reduced to 25 x 10(6), graft survival in the group given GM-CSF-treated cells was prolonged compared with survival in the group given normal cells. Grafts in the group given GM-CSF-treated lymph node cells were rejected in sensitized fashion. When marrow and spleen are separated on a Percoll gradient, the cell active in promoting graft survival is recovered primarily in the 52.5% fraction. The graft-prolonging effect of the 52.5% marrow fraction was not affected by GM-CSF treatment. In contrast, GM-CSF-treated marrow cells in the 60% fraction significantly prolonged graft survival, while normal marrow cells in this fraction had no effect on graft survival. GM-CSF-treated spleen cells in the 52.5% and 60% fractions significantly decreased graft survival compared with normal cells when given at a dose equal to the number of cells recovered from 50 x 10(6) cells. When the dose of fractionated spleen cells was reduced, GM-CSF-treated spleen cells were more effective than normal cells in prolonging graft survival. These results indicate that GM-CSF activates a cell in marrow that promotes graft survival. This cell is recovered in the 60% Percoll fraction. In contrast, GM-CSF appears to affect two cell populations in spleen, one beneficial and one detrimental to graft survival. The predominant effect depends on the dose of spleen cells that is given.
Monaco
A P
AP
Department of Surgery, Harvard Medical School, New England Deaconess Hospital, Boston, MA 02215.
Wood
M L
ML
Gottschalk
R
R
Seiler
F R
FR
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D000961:Antilymphocyte Serum / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D000961:Antilymphocyte Serum; D018800:Thy-1 Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor