Cancer Immunology, Immunotherapy

, Volume 40, Issue 2, pp 103–108

The induction of bacillus-Calmette-Guérin-activated killer cells requires the presence of monocytes and T-helper type-1 cells

  • Andreas Thanhäuser
  • Andreas Böhle
  • Berthold Schneider
  • Norbert Reiling
  • Taila Mattern
  • Martin Ernst
  • Hans-Dieter Flad
  • Artur J. Ulmer
Original Article BCG, BAK Cells, Monocytes, T-Helper Cells, Bladder Tumour, Macrophages, NK Cells

DOI: 10.1007/BF01520291

Cite this article as:
Thanhäuser, A., Böhle, A., Schneider, B. et al. Cancer Immunol Immunother (1995) 40: 103. doi:10.1007/BF01520291

Abstract

Previously we have described the induction of MHC-unrestricted killer cells against bladder tumour cells by bacillus Calmette-Guérin (BCG), termed BCG-activated killer (BAK) cells. In the present paper we deal with the accessory-cell requirement for the activation of BAK cells. We show that monocytes are required for activating BAK cells, since no cytotoxicity can be induced in the absence of monocytes. Therefore, these phagocytes may represent the first step during the activation cascade of BAK cells. Furthermore, the presence of CD4+ T cells was essential for generating BAK cells: depleting peripheral blood mononuclear cells of CD4 cells prior to stimulation with BCG abolished the cytotoxicity against bladder tumour cells. Experiments with monoclonal antibodies (mAb) neutralizing the activity of either interleukin-2 (IL-2) or interferon γ (IFNγ) underlined the importance of these cytokines: both mAb blocked the induction of BAK cells. Since both cytokines are related to the so-called Th1 pattern of T cells, we consider the second step of the generation of BAK cells as follows: monocytes presenting antigens of BCG trigger Th1-like cells in a preferred manner. These Th1-like T cells secrete IL-2 and IFNγ and, thus, activate the BAK effector cells. Since CD4+ cells are dominant in the cells infiltrating the bladder wall after intravesical instillation of BCG in vivo, we postulate an important role for the Th1 subpopulation. We further postulate that the occurrence of macrophages in this infiltrate seems to be significant in the maintenance of the relapse-free state of the patient.

Key words

BCG BAK cells Monocytes T-helper cells Bladder tumour Macrophages NK cells 

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Andreas Thanhäuser
    • 1
  • Andreas Böhle
    • 2
  • Berthold Schneider
    • 2
  • Norbert Reiling
    • 1
  • Taila Mattern
    • 1
  • Martin Ernst
    • 1
  • Hans-Dieter Flad
    • 1
  • Artur J. Ulmer
    • 1
  1. 1.Department of Immunology and Cell BiologyForschungsinstitut BorstelBorstelGermany
  2. 2.Department of UrologyMedical University of LübeckLübeckGermany

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