Cell cycle assessment of adoptive transferred lymphokine activated killer cells.
The use of lymphokine activated killer (LAK) cells for adoptive transfer therapy has been reported from number of clinical trials. To our knowledge, however, there has been no report concerning the cell cycle progression of LAK cells. Thus, for the present study we have attempted to examine the LAK cell cycle either before or after transfer. In vitro and in vivo analyses of LAK cells labeled with bromodeoxyuridine (BrdU) were carried out using two-parameter flow cytometries of their nuclear staining using fluorescein isothiocyanate(FITC)-conjugated anti-BrdU antibody and propidium iodide (PI). The in vitro growth of BrdU-positive cells showed the cells to divide once in the S phase, continue to the G2-M phase and return to the G0-G1 phase with a similar pattern after 48 or 72 h culture. They formed a definite subpopulation and were of phenotypes, thy-1.2 (+), Lyt-1.1 (-), Lyt-2.1 (+), L3T4 (-) and AGM1 (+). The percentage of BrdU-positive cells decreased significantly (P < 0.05) when treated with complement plus anti-thy-1.2, anti-Lyt-2.1 or anti-AGM1 anti-bodies, demonstrating BrdU-labeled LAK cells to have the same phenotype as control LAK cells. As in vitro, the in vivo cell cycle of LAK cells 48 and 72 h after transfer had a similar pattern, and the LAK cells also continued on to the S phase after the first division. The in vivo growth of the LAK cells treated with interleukin-2 (IL-2) was promoted 24 and 48 h after transfer. In conclusion, the present study showed LAK cells to be capable of dividing following transfer and to keep their own phenotypic characteristics; also, that treatment with IL-2 may promote their division. Adoptive transfer therapy seems to be a viable therapeutic method.
Watanabe
R
R
First Department of Surgery, Okayama University Medical School.
Tanaka
N
N
Naomoto
Y
Y
Moreira
L F
LF
Orita
K
K
D000818:Animals; D001973:Bromodeoxyuridine; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005677:G(M1) Ganglioside / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D007518:Isoantibodies / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D007518:Isoantibodies; C029805:Lyt antibodies; C035678:anti-Thy antibody; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003165:Complement System Proteins; D001973:Bromodeoxyuridine