M. bovis-BCG elicits memory CD8+ T cell responses to mycobacteria in cattle (43.53)

Abstract

Abstract Tuberculosis (TB) remains one of the leading causes of death due to infectious disease. Current aims to improve vaccines against TB have focused on enhancing immunity conferred by the attenuated M. bovis BCG (BCG) vaccine. The design of a vaccine to specifically boost the protective features of BCG requires a greater understanding of the immune response induced by BCG vaccination. In this work we show that vaccination with BCG induces a population of CD8+CD45RO+ T cells that proliferate, produce IFN-gamma, up-regulate expression of perforin and granulysin, and lyse BCG-infected macrophages, following antigen specific stimulation. To determine whether a similar response could be detected in vivo, vaccinated animals were re-inoculated intradermally with BCG or PBS eight weeks after primary BCG vaccination. Draining lymph nodes were removed 3 days after the second inoculation for analysis by immunofluorescence and confocal microscopy for the presence of activated CD8+ T cells. Clusters of CD8+CD3+perforin+ cells were readily detectable in lymph nodes from animals re-inoculated with BCG but absent in the animals given PBS in the second inoculum. These results suggest that the memory CD8+ T cells induced by BCG vaccination have the capacity to mount secondary responses to mycobacteria in vivo. Support for these studies was provided by the BBSRC, DEFRA and the Jenner Institute.