Effects of cholera toxin on the lymphoid system. III. In vivo generation of cytotoxic lymphocytes.

Cytotoxic T lymphocytes (CTL) were generated in the spleen by subcutaneous inoculation of EL-4 leukaemia cells (H-2b) into C3H/He mice (H-2k). (1) Cytotoxicity of spleen cells was profoundly suppressed by an intravenous injection of 1 microgram cholera toxin on the day of tumor inoculation. Tumors continued to grow progressively. (2) Differentiation of memory cells to mature CTL was suppressed by cholera toxin injection on the day of booster inoculation of EL-4 cells. The tumors grew progressively in immune mice given cholera toxin on the day of the booster. (3) In vitro treatment of CTL with cholera toxin suppressed the expression of their cytotoxic activity to a considerable extent. However, tumors regressed very rapidly after rechallenge to immune mice carrying CTL, even when cholera toxin was injected on the day of rechallenge. Cholera toxin suppressed not only the functional expression of CTL but also the induction phase of CTL generation.