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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2001-11-0106.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 4049-4058
IMMUNOBIOLOGY
Antagonistic effect of NK cells on alternatively activated
monocytes: a contribution of NK cells to CTL
generation
Anja B. Geldhof,
Jo A. Van Ginderachter,
YuanQing Liu,
Wim Noël,
Geert Raes, and
Patrick De Baetselier
From the Department of Cellular Immunology, Flanders
Interuniversity Institute for Biotechnology, Vrije Universiteit
Brussel, St Genesius Rode, Belgium.
Natural killer (NK) cells fulfill essential accessory functions for
the priming of antigen-specific cytotoxic T lymphocytes (CTLs).
On the basis of a NKG2D-ligand-positive tumor model, we obtained
results implicating NK-mediated regulatory as well as NK-mediated
cytolytic activities in the initiation and persistence of CTL activity.
Indeed, CD8+ T-cell-dependent tumor rejection requires NK
cell function in vivo, because tumors will progress both on depletion
of NK cells or in the absence of optimal NK activity. Here we provide
evidence that the absence of NK cells during subcutaneous tumor growth will abrogate generation of antitumor CTL responses and that this process can be linked to the expansion of alternatively activated monocytes. Indeed, our in vitro studies demonstrate that in splenic cultures from NK-deficient tumor-bearing mice, lack of type
1-associated cytokines correlates with the presence of type 2 (alternatively activated) monocytes and the production of type 2 cytokines. Furthermore, these type 2 monocyte-containing splenic
adherent populations potently suppress subsequent memory CTL
restimulation. We evaluated the role of NK lytic effector functions in
the efficient switch of the immune system toward classical (type 1)
activation by including differentially activated monocytic populations
as targets in cytotoxicity assays. The results indicate that the
accessory function of NK cells depends partially on the ability of
activated NK cells to preferentially engage type 2 antigen-presenting
cells. Thus, when the immune system tends to be type 2 oriented, NK
cells can drive an efficient type 2  type 1 switch in the population
of antigen-presenting cells to provide signaling for the generation of CTLs.
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