Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease.
Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients.
Azuma
E
E
Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI 48202.
Yamamoto
H
H
Kaplan
J
J
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007113:Immunity, Innate / Q000528:radiation effects; D007116:Immunization, Passive; D007375:Interleukin-1 / Q000494:pharmacology; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D007519:Isoantigens; D011994:Recombinant Proteins