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

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 T_H1 and T_H2 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 T_H1 and T_H2 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 T_H2-type diseases with monocyte-stimulating agents, e.g. (G)M-CSF.

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Specjalista dermatolog i wenerolog, alergolog Kraków