Recruitment of dendritic cells and macrophages during T cell-mediated synovial inflammation

Adoptive transfer of adjuvant-induced arthritis was used in this study to examine local macrophages and dendritic cells (DCs) during T cell-mediated synovial inflammation. We studied the influx of CD11b(+)CD11c(+ )putative myeloid DCs and other non-lymphoid CD45(+ )cells into synovium-rich tissues (SRTs) of the affected hind paws in response to a pulse of autoreactive thoracic duct cells. Cells were prepared from the SRTs using a collagenase perfusion-digestion technique, thus allowing enumeration and phenotypic analysis by flow cytometry. Numbers of CD45(+ )cells increased during the first 6 days, with increases in CD45(+)MHC (major histocompatibility complex) II(+ )monocyte-like cells from as early as day 3 after transfer. In contrast, typical MHC II(- )monocytes, mainly of the CD4(- )subset, did not increase until 12 to 14 days after cell transfer, coinciding with the main influx of polymorphonuclear cells. By day 14, CD45(+)MHC II(hi )cells constituted approximately half of all CD45(+ )cells in SRT. Most of the MHC II(hi )cells expressed CD11c and CD11b and represented putative myeloid DCs, whereas only approximately 20% were CD163(+ )macrophages. Less than 5% of the MHC II(hi )cells in inflamed SRT were CD11b(-), setting a maximum for any influx of plasmacytoid DCs. Of the putative myeloid DCs, a third expressed CD4 and both the CD4(+ )and the CD4(- )subsets expressed the co-stimulatory molecule CD172a. Early accumulation of MHC II(hi)CD11c(+ )monocyte-like cells during the early phase of T cell-mediated inflammation, relative to typical MHC II(- )blood monocytes, suggests that recruited monocytes differentiate rapidly toward the DC lineage at this stage in the disease process. However, it is possible also that the MHC II(hi)CD11c(+ )cells originate from a specific subset of DC-like circulating mononuclear cells.