PROMOTION OF CYTOTOXIC T-CELL GENERATION IN MIXED LEUKOCYTE-CULTURE BY PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C FROM BACILLUS-THURINGIENSIS

Phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus th uringiensis, which cleaves phosphatidylinositol or glycosylphosphatidy linositol on the external cell surface to generate a second messenger for intracellular signal transduction (S. Rahman et al., FEBS Lett. 30 3:193-196, 1992), was found to preferentially promote the generation o f alloantigen-specific cytotoxic T lymphocytes in mixed leukocyte cult ure. PIPLC affected an early stage of cytotoxic T-lymphocyte activatio n in culture, and there was no evidence of any soluble cellular mediat ors of this PIPLC action. PIPLC neither enhanced overall cell prolifer ation nor noticeably promoted interleukin-2 and -4 production in mixed leukocyte culture. The relative population size of Ly-2(+) T cells wa s increased, however, in a late mixed leukocyte culture with PIPLC. In addition, PIPLC enhanced an anti-CD3 monoclonal antibody-induced earl y increase in [Ca2+](i). These results suggest a new parasite (bacteri um)-oriented mechanism for enhancing antigen-driven host cytotoxic T-l ymphocyte immunity which does not include promotion of interleukin-2 p roduction.