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In vivo or in vitro modulating effects of vincristine on the generation of allogeneic cytotoxic lymphocytes in vitro.

Cytotoxic lymphocytes carrying the H-2(i5) haplotype were generated in vitro against alloantigens specified by the IC-S-G-D regions of H-2. Responder lymphocytes were collected from donors B10.A(5R) non-treated or treated with 3 or 0.6 mg/Kg, ip of Vincristinee (VCR) and incubated with irradiated B10 spleen cells. High doses of VCR produced depression of the cytotoxic response (CR), whereas 0.6 mg/Kg of the drug produced substantial increase of the response. Further experiments were conducted adding VCR in vitro to the tissue culture during the generation of cytotoxic lymphocytes. Depression of CR occurred following treatment with high concentrations of VCR. On the other hand, marked increase of CR was found using responder lymphocytes treated in vitro with low concentrations (i.e. 0.016 - 0.0032 microgram/ml) of the drug. The mechanism of VCR-induced enhancement of CR has not been elucidated. However, the present data show the possibility of increasing host immune responses by treatment of donor mice or of responder lymphocytes with VCR at selected doses or concentrations.