Enrichment and Characterization of Dendritic Cells from Rat Renal Mesangium

Abstract

Dendritic cells (DC) initiate primary immune reactions and are distributed throughout most tissues. The most potent DC population of the kidney has long been suggested to reside within the glomerular mesangium. Using LEW.1A rats, we enriched and characterized such low-density cells. Mesangial DC generally exhibited round to oval cell bodies and cytoplasmic veils. Phenotypically, these cells were 100% OX-6 þþ , 45% OX-42 þþ , 35% ED1 low , 10% OX-62 low , and negative for ED2 and a-naphtylbutyrate esterase. Introducing a new monoclonal antibody, R3, which stains a subset of splenic DC, we showed strong antigen expression on 60% of mesangial DC. Correlating cell populations were detected immunohistochemically. Functionally, mesangial DC potently stimulated allogeneic mixed leucocyte reactions, but did not phagocytose opsonized Escherichia coli. In addition to their striking phenotypic similarity with autologous splenic DC, mesangial DC exhibited 88% of the allostimulatory activity of splenic DC. Calculation indicated approximately two mesangial DC per glomerulum. We suggest that these cells comprise different maturation-dependent subsets. The OX-62 integrin especially appears to be expressed only on mature mesangial DC, which may correlate to lymphoid veiled cells or interdigitating DC. An employment of mesangial DC in experimental models of acute allograft rejection or glomerulonephritis is discussed. R. Gieseler,

Flt3 ligand generates morphologically distinct semimature dendritic cells in ovalbumin-sensitized mice

“…We observed comparatively more dendrites in myeloid DCs and OVA-sensitized and challenged DCs than in plasmacytoid DCs or PBS-or FL-treated groups. Although a direct correlation has not been shown in the current study, many previous studies by others have shown that mature DCs, as defined by their pronounced display of motile dendrites, have a high capacity to induce proliferative responses in resting T cells (Maraskovsky et al, 1996;Gieseler et al, 1997;Thurnher et al, 1997).…”

Identification of a bone marrow-derived CD8αα+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis

“…In contrast, this new type of DC invades the inflamed glomeruli specifically. Second, numerous previous studies have described different types of DCs in autoimmune diseases, including several types of GNs [12][13][14][15][16][17]32]. DCs reported in those studies generally promote or initiate T cell-mediated pathogenesis through their APC function.…”

“…Previous studies in humans suggest a role of DCs in promotion of GN pathogenesis [11]. More recent studies were based on animal models for various types of GN [12][13][14][15][16][17]. One study characterized DCs derived from BM in GN or in healthy mice and found CD11 ϩ cells in the renal interstitium, which may activate T cells [12].…”

“…One study characterized DCs derived from BM in GN or in healthy mice and found CD11 ϩ cells in the renal interstitium, which may activate T cells [12]. A potential DC with the phenotype of OX6 (MHC class II) ϩ OX42 (CD11b/c) ϩ from renal mesangium of healthy rats has been described [13]. The authors suggested that those DCs may play roles in GN pathogenesis or acute allograft rejection.…”

Dendritic cells and macrophages in the kidney: a spectrum of good and evil

“…The renal DC population was thought initially to localize to the glomerular compartment and thus mediate the pathogenesis of glomerulonephritides. This assumption was supported by isolation of rodent glomerular cells phenotypically distinct from mesangial cells, that expressed MHC class II (Ia) and exhibited T cell allostimulatory capacity in primary mixed leukocyte cultures 39–42. Concurrent rodent and human studies confirmed the presence of MHC class II + cells within the cortical interstitium 43, 44.…”