Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease
- Wayne State Univ. School of Medicine, Detroit, MI (USA)
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.
- OSTI ID:
- 5601230
- Journal Information:
- Journal of Immunology; (USA), Journal Name: Journal of Immunology; (USA) Vol. 143:5; ISSN JOIMA; ISSN 0022-1767
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIGENS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
BONE MARROW CELLS
CELL CULTURES
CHIMERAS
CLONE CELLS
CONNECTIVE TISSUE CELLS
FUNCTIONS
GRAFT-HOST REACTION
GROWTH FACTORS
IMMUNITY
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MICE
MITOGENS
MOSAICISM
ORGANIC COMPOUNDS
PHENOTYPE
PROTEINS
RADIATION CHIMERAS
RODENTS
SOMATIC CELLS
SPLEEN CELLS
TRANSPLANTS
VERTEBRATES