Activation of an interleukin‐4 mRNA‐producing population of peripheral blood mononuclear cells after infection with Mycobacterium bovis or vaccination with killed, but not live, BCG

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Abstract
Summary: This study examines the expression of mRNA for the Th2 cytokine, interleukin‐4 (IL‐4). Peripheral blood mononuclear cells from deer infected with Mycobacterium bovis or vaccinated with live or killed M. bovis bacillus Calmette–Guérin (BCG) were cultured with mycobacterial antigens. IL‐4 mRNA production was assayed using the polymerase chain reaction. Elevated levels of IL‐4 mRNA were detected in response to at least one antigen preparation in all animals infected with M. bovis as compared with none of the non‐infected control animals. After a primary immunization, elevated levels of IL‐4 mRNA were detected in only a proportion of vaccinated animals and this did not correlate with whether the vaccine was live BCG or killed BCG in oil. After boosting, all the animals vaccinated with killed BCG in oil exhibited elevated IL‐4 mRNA production whereas none of the animals vaccinated with live BCG showed elevated levels. The data suggest that IL‐4 is turned off during the immune response to live BCG, that boosting of low‐dose live BCG vaccine may be required to ‘imprint’ this signal and that this may be important in the development of protective immunity to tuberculosis. Killed BCG in adjuvant is not protective and as with experimental infection with virulent M. bovis it failed to switch off the IL‐4 response. IL‐4 may be useful as a diagnostic tool and as an in vitro marker of vaccine efficacy.