Selective expansion of perforin-positive CD8 T cells by immature dendritic cells infected with live Bacillus Calmette-Guérin mycobacteria

Abstract: Live, but not dead Bacillus Calmette-Guérin (BCG) is partially protective against infection by Mycobacterium tuberculosis, which causes a dis-ease with high mortality in immune compromised individuals. We have shown that uptake of BCG in-duces maturation of immature dendritic cells (DCs) regardless of the viability of the bacteria. Impor-tantly, when T cells are cocultured with live BCG-infected DCs, the proportion of CD45RA perforin CD8 T cells is markedly expanded markedly; how-ever, little expansion is seen when T cells are cocul-tured with DCs harboring heat-killed BCG. The di-rect contact of T cells with live BCG-infected DCs was required for the expansion of perforin CD8 T cells. These CD8 T cells demonstrated a high level of killing activity against BCG-infected macrophages. There was little contribution of cytokines, including IFN-, TNF-, and IL-12, to the expansion of CD8 T cells by live BCG-infected DCs. We found that the interaction between BCG-infected DCs and CD8 T cells through CD40/CD40L was crucial for the ex-pansion and maturation of CD8 T cells, the process of which was CD4-independent. In contrast, blocking the CD58/CD2 but not the CD40/CD40L interaction reduced production of IFN- without affecting the maturation of CD8 T cells. This indicates that the production of IFN- and perforin by CD8 T cells is mediated by distinct signals delivered from BCG-in-fected DCs. Thus, BCG-specific CD8 CTL memory cells may be maintained for a long period of time in BCG-vaccinated hosts, and these cells could mature rapidly into effectors through the potent antigen-presenting function of DCs upon mycobacteria