Application of monoclonal antibodies to the characterization of cells eluted from human articular cartilage. Expression of Ia Antigens in Certain Diseases and Identification of an 85‐kD Cell Surface Molecule Accumulated in the Pericellular Matrix

Abstract

Ia antigens were strongly expressed on a considerable proportion of cells eluted from the damaged articular cartilages of certain individuals with osteoarthritis, rheumatoid arthritis, traumatic arthritis, or from osteochondromas. In contrast, Ia antigens were found on less than 1% of cells eluted from the more normal appearing cartilage of certain other patients with osteoarthritis, rheumatoid arthritis, osteonecrosis, femoral neck fractures, an enchondroma, and a chondrosarcoma. The cell preparations obtained from these latter individuals consisted of clusters of 1-4 chondrocytes embedded in a surrounding island of the pericellular matrix, whereas as in the samples that yielded Iapositive cells, many chondrocytes were isolated as free cells without a surrounding matrix. The Ia antigens were detected primarily on this latter cell population, suggesting that their expression might indicate a chondrocyte activated to alter its surrounding matrix. The cytologic features of the Ia-positive cells were indistin- guishable from those of the Ia-negative chondrocytes. All eluted cells lacked antigens of the monocyte, B cell, or T cell lineages. An antigen detected by the monoclonal reagent M+R-17 was identified on the membrane of large numbers of chondrocytes, both with and without the pericellular matrix, indicating that the matrix in these preparations was permeable to molecules the size of antibodies. A monoclonal antibody 83c2, demonstrated to react with an 85-kD surface molecule expressed on certain fibroblastoid and other cells, detected an antigen present on the majority of normal chondrocytes and in varying percentages of cartilage cells obtained from patients with osteoarthritis or rheumatoid arthritis. Of special interest, the periphery of the pericellular matrix was stained by this reagent in an irregularly distributed ring-like zone, suggesting that the 83c2 molecule was shed into the matrix from the cell surface and accumulated in these areas.The articular cartilage is a highly specialized tissue characterized by a relatively small number of cells embedded in an avascular extracellular matrix produced and maintained by the chondrocytes (I). The chondrocytes are usually found in clusters of several cells in a specialized region of the ground substance, the lacunar or pericellular matrix (1).Degenerative and inflammatory joint diseases are characterized by the loss of articular cartilage reflecting the operation of a variety of mechanisms including metabolic and mechanical factors, the destruction caused by enzymes released from synovial cells upon direct cell contact with the cartilage surface (2), and the release of mediators stimulating the chondrocytes to actively resorb their own matrix (2-5).

Cellular responses to human chondrocytes: absence of allogeneic responses in the presence of HLA-DR and ICAM-1

“…However, studies with transgenic mice which express MHC genes in pancreatic islel cells have shown variable resuUs and no consistent evidence of autoimmunity to these tissues [47.48], Normalchondrocylesdo not express class II. but class II posi(ive eells have been reported in ()A and RA cartilage [16] and after IFN-y stimulalion [17], Our resuUs confirm this latter observation and show that IL-1^ may also induce these molecules but at a low intensity of expression. IL-1 production by RA synovium has been shown by others [49] lo correlate well with immunohistochemical staining for DR in synovial tisucs.…”

“…Aberrant DR expression may be induced by viral or other environmental agents and may be mediated by interferon-gamma (IFN-y) released following the activation of T lymphocytes. This aberrant DR expression, on chondrocytes for example, couid lead to the presentation of autoantigens to autologous T cells with subsequent tissue damage, HLA-DR molecules are not found on articular chondroeytes from normal articular eartilage but have been demonstrated in disease states [16] and after stimulation of normal ehondrocyles by IHN-y [I7[. Eflective T cell stimulation requires the presence of accessory cells and cytokines [l«.iy].…”

Immune response by host after allogeneic chondrocyte transplant to the cartilage

“…Expression of MHC class II (formerly Ia) antigens has been demonstrated in human articular cartilage chondrocytes from patients with rheumatoid arthritis and osteoarthritis, while normal chondrocytes were class II-negative (Burmester et al, 1983;Lance et al, 1993). In tracheal cartilage, only a few chondrocytes express class II antigens (Shaari et al, 1998).…”

Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus

“…Addressing these limitations, we focused on the development of 3-D culture models that would allow us to study the inflammatory joint process in the context of the extracellular matrix and to investigate the contribution of distinct cell populations such as chondrocytes (34,35) …”