Lymphokine-activated killer cells are rejected in vivo by activated natural killer cells.
A 4-h in vivo cytotoxicity assay was used to study the fate of implanted IL-2-generated, lymphokine-activated killer (LAK) cells in mice undergoing an activated NK cell response. 125Iododeoxyuridine-labeled LAK cells were rejected from selected organs of C57BL/6 mice infected with lymphocytic choriomeningitis virus or treated with IL-2 or the IFN inducer poly I:C. This rejection was abrogated by the selective depletion of NK cells with antibodies to asialo-GM1 and NK1.1 Ag. Similar results were noted when LAK cells were generated from the spleens of B and T cell-deficient severe combined immunodeficiency mice and when LAK cells were implanted into severe combined immunodeficiency mice. These data indicate that NK cells activated by virus infections or by IL-2 infusions directly or indirectly eliminate implanted LAK cells. Because LAK cells are used in the treatment of certain human cancers, the strategy of accompanying this therapy with IL-2 infusions should be reassessed in light of these results.
Brubaker
J O
JO
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Chong
K T
KT
Welsh
R M
RM
D000818:Animals; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007223:Infant; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology
D007376:Interleukin-2; D011070:Poly I-C