Non-specific, rapidly generated cytotoxicity in lymphocytes induced by BCG in vitro: no evidence of enhancing effect from preceding interaction between BCG and transitional cell line cells.
OBJECTIVE
To study short-term events in the mechanism of action of BCG with an emphasis on the interaction between BCG and T24 cell line cells.


METHODS
Peripheral blood mononuclear cells (PBMNC) or/and several tumor cell lines were incubated with BCG (Oncotice) using various clinical and subclinical BCG concentrations.


RESULTS
3 h BCG incubation of PBMNC at 10(7) - 5*10(5) CFU/ml., followed by a 4 h cytotoxicity test, resulted in a significant augmentation of cytotoxicity of PBMNC against T24 cells, and the augmentation was almost significant at 10(5) CFU/ml. Overnight BCG incubation of PBMNC further augmented that cytotoxicity at all concentrations down to 10(4) CFU/ml. The minimum overall time (incubation with BCG + cytotoxicity test), where stimulation of PBMNC could be detected, was only 4 h. The BCG enhanced cytotoxicity of PBMNC could be demonstrated against all the tested cell line cells in a 4 h cytotoxicity test by using a preceding overnight BCG incubation of PBMNC, and against the majority of the cell lines by using a preceding 3 h BCG incubation of PBMNC. No convincing evidence was obtained to support the hypothesis that BCG should be first processed by T24 cells to make these cells more susceptible to cell mediated lysis by PBMNC.


CONCLUSIONS
Clinical and subclinical concentrations of BCG are directly stimulatory to PBMNC, which become, in a minimum time of a few hours, more capable of killing tumor cells, without a need for preceding interaction between BCG and tumor cells.
Kaasinen
E S
ES
Hyvinkää Hospital, Finland.
Harju
L M
LM
Alfthan
O S
OS
Timonen
T T
TT
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001500:BCG Vaccine / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine