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(Journal of Leukocyte Biology. 2002;72:115-124.)
© 2002 by Society for Leukocyte Biology

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

Yasuko Tsunetsugu-Yokota^*, Hideto Tamura, Mikiko Tachibana, Kiyoyuki Ogata, Mitsuo Honda and Toshitada Takemori^*

^* Department of Immunology and
The First Group of AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan; and
The Third Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo, Japan

Correspondence: Yasuko Tsunetsugu-Yokota, M.D., Ph.D., Department of Immunology, National Institute of Infectious Diseases, 1-23-1, Toyama-cho, Shinjuku-ku, Tokyo 162-8640, Japan. E-mail: yyokota{at}nih.go.jp

Live, but not dead Bacillus Calmette-Guérin (BCG) is partially protective against infection by Mycobacterium tuberculosis, which causes a disease with high mortality in immune compromised individuals. We have shown that uptake of BCG induces maturation of immature dendritic cells (DCs) regardless of the viability of the bacteria. Importantly, when T cells are cocultured with live BCG-infected DCs, the proportion of CD45RA^- perforin⁺ CD8⁺ T cells is markedly expanded markedly; however, little expansion is seen when T cells are cocultured with DCs harboring heat-killed BCG. The direct 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 expansion 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-infected 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 mycobacterial infection.

Key Words: live and dead BCG • maturation of DCs • IFN- • CD40/CD40L • CTL

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