Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation
Several reports describe regulatory interactions between NK cells and CTLs. We addressed the issue of NK participation in the early anti-tumor defense by inoculating α-ASGM-1 treated mice with BW-Sp3 T lymphoma. Rejection of BW-Sp3 depends on strong CTL responses. Our results demonstrated that (i) N...
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doaj-0c7348469f3445cfb5d7b2c87395b02e2020-11-24T23:31:03ZengHindawi LimitedClinical and Developmental Immunology1740-25221740-25302003-01-01102-4718110.1080/10446670310001626580Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL GenerationAnja B. Geldhof0Jo A. van Ginderachter1Yuanqing Liu2Wim Noël3Patrick de Baetselier4Laboratory of Cellular Immunology, Free University of Brussels, Flemish Interuniversity Institute for Biotechnology, B-1640 St.-Genesius Rode, BelgiumLaboratory of Cellular Immunology, Free University of Brussels, Flemish Interuniversity Institute for Biotechnology, B-1640 St.-Genesius Rode, BelgiumLaboratory of Cellular Immunology, Free University of Brussels, Flemish Interuniversity Institute for Biotechnology, B-1640 St.-Genesius Rode, BelgiumLaboratory of Cellular Immunology, Free University of Brussels, Flemish Interuniversity Institute for Biotechnology, B-1640 St.-Genesius Rode, BelgiumLaboratory of Cellular Immunology, Free University of Brussels, Flemish Interuniversity Institute for Biotechnology, B-1640 St.-Genesius Rode, BelgiumSeveral reports describe regulatory interactions between NK cells and CTLs. We addressed the issue of NK participation in the early anti-tumor defense by inoculating α-ASGM-1 treated mice with BW-Sp3 T lymphoma. Rejection of BW-Sp3 depends on strong CTL responses. Our results demonstrated that (i) NK cells are a prerequisite for efficient CTL generation and (ii) the absence of NK cells favors the outgrowth of alternatively activated macrophages that can suppress CTL restimulation. In vitro studies demonstrate that in splenic cultures from NK-deficient, tumor-bearing mice, the presence of alternatively activated macrophages correlates with a lack of Type 1 cytokines, while the production of Type 2 cytokines is promoted. Provision of the Type 1 cytokine, IFN-γ can boost overall CTL activity but does not revert the dominance of arginase producing adherent cells in the NK-deficient CTL cultures. The role of NK effector functions in the efficient switch of the immune system towards Type 1 activation was evaluated in cytotoxicity assays. The results indicate that the accessory function of NK can depend at least partially on their ability to preferentially engage arginase-producing cells, suggesting that NK/macrophage lytic interactions might be involved in the switch from Type 2 to Type 1-dependent immune responses.http://dx.doi.org/10.1080/10446670310001626580 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anja B. Geldhof Jo A. van Ginderachter Yuanqing Liu Wim Noël Patrick de Baetselier |
spellingShingle |
Anja B. Geldhof Jo A. van Ginderachter Yuanqing Liu Wim Noël Patrick de Baetselier Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation Clinical and Developmental Immunology |
author_facet |
Anja B. Geldhof Jo A. van Ginderachter Yuanqing Liu Wim Noël Patrick de Baetselier |
author_sort |
Anja B. Geldhof |
title |
Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation |
title_short |
Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation |
title_full |
Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation |
title_fullStr |
Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation |
title_full_unstemmed |
Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation |
title_sort |
ablation of nk cell function during tumor growth favors type 2-associated macrophages, leading to suppressed ctl generation |
publisher |
Hindawi Limited |
series |
Clinical and Developmental Immunology |
issn |
1740-2522 1740-2530 |
publishDate |
2003-01-01 |
description |
Several reports describe regulatory interactions between NK cells and CTLs. We addressed the issue of NK participation in the early anti-tumor defense by inoculating α-ASGM-1 treated mice with BW-Sp3 T lymphoma. Rejection of BW-Sp3 depends on strong CTL responses. Our results demonstrated that (i) NK cells are a prerequisite for efficient CTL generation and (ii) the absence of NK cells favors the outgrowth of alternatively activated macrophages that can suppress CTL restimulation. In vitro studies demonstrate that in splenic cultures from NK-deficient, tumor-bearing mice, the presence of alternatively activated macrophages correlates with a lack of Type 1 cytokines, while the production of Type 2 cytokines is promoted. Provision of the Type 1 cytokine, IFN-γ can boost overall CTL activity but does not revert the dominance of arginase producing adherent cells in the NK-deficient CTL cultures. The role of NK effector functions in the efficient switch of the immune system towards Type 1 activation was evaluated in cytotoxicity assays. The results indicate that the accessory function of NK can depend at least partially on their ability to preferentially engage arginase-producing cells, suggesting that NK/macrophage lytic interactions might be involved in the switch from Type 2 to Type 1-dependent immune responses. |
url |
http://dx.doi.org/10.1080/10446670310001626580 |
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