Cellular Analysis of Cutaneous Granuloma induced by Antigen-binding Agarose Particle and MDP

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We examined immune cells and cytokine production in murine cutaneous granulomas induced by antigen-binding agarose particles and MDP. A few number of CD3+ cells are present in the center of granulomas and their surrounding areas. Almost same numbers of CD4+ and CD8+ cells are distributed. On the other hand, CD14+ monocytes are main cells of the granuloma, but tissure macrophages which are positive for MMGL were not present in the center of the granulomas. IFN-γ+ cells were more predominantly distributed than IL-4+ cells, suggesting that the induced cutaneous granuloma had a property of TH1 type reaction. To examine the propety of precursor cells of monocyte-macrophage lineage cells in the granulomas, the folowing cells were prepared from GFP-transgeneic mice, 1) peripheral monocytes, 2) macrophages induced by culturing monoctes, 3) MMGL+ dermal macrophages in normal skin, 4) peritoneal macrophages, 5) bone marrow cells, 6) dendritic cells induced from bone marrow cells with GM-CSF/IL-4. These cells were administered subcutaneously or intraveneously into granuloma-bearing mice. GFP+ cells were found in the granuloma only when freshly isolated bone marrow cells were injected. To investigate the response ofepithelioid cells in granuloma to cytokines, epithelioid cells were riched by eliminating CD3+ cells, B220+ cells and MMGL+ cells in the granulomas. Theses cells responded to IFN-γ and IL-3 but not to IL-13 or IL-10. These results suggest that infiltrating cells from bonw marrows consist of cutaneous granulomas induced by antigen-binding agarose particles and MDP, and that IFN-γ and EL-3 are a key factor for the formation of granulomas.