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 IIhi cells constituted approximately half of all CD45+ cells in SRT. Most of the MHC IIhi cells expressed CD11c and CD11b and represented putative myeloid DCs, whereas only approximately 20% were CD163+ macrophages. Less than 5% of the MHC IIhi 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 IIhiCD11c+ 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 IIhiCD11c+ cells originate from a specific subset of DC-like circulating mononuclear cells.
Moghaddami
Mahin
M
Arthritis Research Laboratory, Hanson Research Institute, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia, 5000, Australia. mahin.moghaddami@imvs.sa.gov.au
Cleland
Leslie G
LG
Radisic
Gorjana
G
Mayrhofer
Graham
G
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000276:immunology / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology / Q000473:pathology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013585:Synovitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039481:CD11b Antigen; D039521:CD11c Antigen; D015704:CD4 Antigens; C497966:Cd86 protein, rat; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens