Modulatory effect on secondary immune response by different subsets of antigen presenting cells

Radoslaw Spiewak1, Mascha Toebak2, B. Mary E. von Blomberg3, Derk P. Bruynzeel2, Rik J. Scheper3, Susan Gibbs2, Thomas Rustemeyer2

1 Jagiellonian University Medical College, Faculty of Health Care, Institute of Public Health, Krakow, Poland; 2 VU University Medical Centre, Dermatology, Amsterdam, the Netherlands; 3 VU University Medical Centre, Pathology, Amsterdam, the Netherlands.

Source: Spiewak R, Toebak M, von Blomberg BME, Bruynzeel DP, Scheper RJ, Gibbs S, Rustemeyer T. Modulatory effect on secondary immune response by different subsets of antigen presenting cells. In: Valenta R, Akdis C, Bohle B (Eds). EAACI 2006. XXV Congress of the European Academy of Allergology and Clinical Immunology, Vienna, Austria, 10-14 June 2006, 288 (Abstract 1033).

 

Background: Peripheral blood mononuclear cells that act as antigen presenting cells (APC) or influence in another way the initiation of secondary responses to antigens are: monocytes, B lymphocytes, myeloid dendritic cells and plasmacytoid dendritic cells. In order to assess whether newly defined subsets of APC exert stimulatory or regulatory effects in protein-antigen handling, we studied immune responses in cultures of PBMC depleted of one or more APC types.

Methods: PBMC of 5 healthy, tetanus-immunised volunteers were analysed for proliferation and TH1 and TH2 activation in response to tetanus toxoid. The depletion of particular APC types: monocytes (CD14-positive), B lymphocytes (CD19), myeloid (BDCA-1) and plasmacytoid (BDCA-2) dendritic cells, was done with magnetic separation and purity was checked with flow cytometry. Proliferative response to tetanus toxoid was measured through 3H-thymidine incorporation. Activation of TH1 and TH2 was assessed through IFN-γ and IL-5 secretion (ELISA).

Results: Depletion of any of the APC types alone caused no or moderate decrease of proliferation (at least 60% of activity preserved). After leaving only one type of APC in cultures, proliferation was down to 17-36%. Depletion of all four APC types further reduced proliferation to 14%. Similar pattern was seen for IFN-γ secretion. A different picture was observed regarding IL-5: after depletion of CD14(+) cells, the mean IL-5 secretion increased by 251%, whereas a slight increase (26%) was also seen after depletion of BDCA-1(+) APC. In cultures, in which CD14(+) was left as the only APC, IL-5 secretion was lower than in cultures depleted of all APC. In contrast to this, IL-5 production in cultures with BDCA-2(+) APC alone was 9% higher than in the control. The observed differences were statistically significant (Friedman test p<0.001, Kendall's coefficient of concordance: 0.76 for IFN-γ, 0.72 for LPT, and 0.63 for IL-5).

Conclusion: Our results show that protein-antigen presentation is mediated by multiple types of APC, with no or little specialised contributions of currently known APC subsets. The exception is CD14(+) APC, which exert a prominent regulatory effect on IL-5 production. This might provide a hint for a novel therapeutic approach in severe asthma and other TH2-type diseases with monocyte-stimulating agents, e.g. (G)M-CSF.

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Document created: 23 June 2006, last updated: 1 September 2007.