Blood cells that can possibly act as antigen presenting cells (APC) in the initiation of secondary humoral response to proteins are: monocytes, lymphocytes B, monocytoid dendritic cells and plasmacytoid dendritic cells. To assess their actual involvement in this process, we studied immune responses in cultures of PBMC depleted of one or more APC types.
Methods: PBMC of 5 healthy, tetanus-immunised volunteers were cultured with tetanus toxoid as the model antigen. The depletion of particular APC types: CD14(+), CD19(+), BDCA-1(+), and BDCA-2(+) was done by means of magnetic separation and checked with flow cytometry. Proliferative responses to tetanus toxoid were measured through 3H-thymidine incorporation, activation of TH1 and TH2 was measured through IFN-γ and IL-5 secretion (ELISA).
Results: Depletion of any of the APC types alone caused no or only a moderate decrease of proliferation response (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 the response (14% of control). Similar pattern was seen for IFN-γ secretion. Regarding IL-5, a different picture was observed: After depletion of CD14(+), the mean IL-5 secretion increased by 251%, a moderate increase (26%) was also seen after depletion of BDCA-1(+). 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, in cultures with BDCA-2(+) as the exclusive APC, production of IL-5 was still slightly higher (9%) than in the non-depleted cultures.
Discussion: Immune response to soluble proteins depends on antibody production by B cells, which is a TH2-operated process. Our results show that plasmacytoid dendritic cells (BDCA-2) play the major role in the initiation of the response, whereas monocytes (CD14) and monocytoid dendritic cells (BDCA-1) have an inhibitory effect.
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Document created: 20 February 2006, last updated: 1 September 2007.