Lymphokine-activated killer (LAK) cells. I. Differential recovery of LAK, natural killer cells, and cytotoxic T lymphocytes after a sublethal dose of cyclophosphamide.
The effect of a sublethal dose of cyclophosphamide (CTX) administered in vivo on murine natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytotoxic T lymphocytes (CTL) was examined. It was found that such a dose of CTX abolished all of the killer cell responses examined. The recovery of each response was then examined as a function of time. Allogeneic CTL responses were the first to recover and could be generated from spleen cells obtained 6 days after CTX administration. Fresh NK cell activity recovered by days 9 to 12. However, when spleen cells obtained 12 days after CTX administration were cultured with interleukin 2 (IL 2) for 5 days, they lost the ability to lyse YAC-1 cells, suggesting a distinction between "augmented" and "fresh" NK cell activity. H-2-restricted, trinitrophenyl-specific CTL activity could be generated by day 14 after CTX, provided the cultures were supplemented with exogenous IL 2. LAK could not be induced until day 21 post-CTX treatment. These data suggest that LAK precursors, CTL precursors, and NK cells are distinct cell populations. Additionally, this report introduces a model that may be useful in examining the differential contribution of NK and LAK to successful adoptive tumor immunotherapy.
D000818:Animals; D002454:Cell Differentiation; D003520:Cyclophosphamide / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D013997:Time Factors
D008222:Lymphokines; D003520:Cyclophosphamide