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The release of soluble forms of CD80 (sCD80), CD86 (sCD86), and CD83 (sCD83) provide a potentially powerful immunoregulatory mechanism. We therefore investigated the potential presence and relative levels of these molecules in the synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum and SF levels were measured by enzyme-linked immunosorbent assay. Serum levels of sCD80, sCD86, and sCD83 in RA and OA patients were similar to those present in normal donor serum (NDS) and the SF of OA patients. In contrast, when compared with NDS and OA SF levels, almost all RA SF samples had elevated sCD83 levels (32/35, >0.63 ng/ml) and a substantial proportion had elevated sCD80 (13/29, >0.22 ng/ml) or sCD86 (16/33, >2.31 ng/ml) levels. Analysis of matched pairs of serum and SF from RA patients demonstrated that the SF/serum ratio for sCD80 (95% CI = 1.7-3), sCD86 (95% CI = 1.5-3.1), and sCD83 (95% CI = 3.6-7.8) levels was >1 in almost all patients. In conclusion, this study shows that the SF from almost all RA patients contain elevated levels of sCD83 and the majority of these samples also contain elevated levels of sCD80 and/or sCD86. These molecules may play a role in modulating immune responses within the rheumatoid joint.

Despite the unique functions of dendritic cells (DC), only two cell surface antigens (CMRF-44 and CD83) with relatively restricted expression on human DC have been described to date. We describe a third mAb, CMRF-56, which recognizes another DC early activation/differentiation antigen with limited expression on other haemopoietic cell populations. Circulating blood leukocytes did not express the CMRF-56 antigen and following either in vitro culture or activation of PBMC populations. CMRF-56 antigen expression was detected only on DC and a subpopulation of CD19(+) lymphocytes. Circulating blood DC were CMRF-56(-) but induced expression within 6 h of in vitro culture. This, together with the finding that tonsil and synovial fluid DC upregulate the antigen following short-term in vitro culture, confirmed that CMRF-56 recognizes an early activation antigen on DC. Isolated Langerhan's cells, dermal DC, migratory dermal DC and monocyte derived DC (GM-CSF/IL-4/TNF alpha) also espress the CMRF-56 antigen antigen modulation studies demonstrated that the amount of cell surface bound CMRF 56 and CMRF-44 (but not CD83) mAb was dramatically reduced by short-term incubation at 37 degrees C. This effect was not due to internalization and the reduction in CMRF-56 binding was a reversible temperature-dependent process. In contrast, the decrease in CMRF-44 binding was irreversible, suggesting that following ligation the CMRF-44 antigen undergoes an irreversible conformational change or shedding at 37 degrees C. Western blotting confirmed that CMRF-56 recognizes a previously undescribed 95 kDa activation antigen whose cellular distribution and expression kinetics overlaps with, but is clearly distinguishable from, that that of the CD83 and CMRF-44 antigens. CMRF-56 therefore provides a useful additional marker for studies on human DC.

Despite the unique functions of dendritic cells (DC), only two cell surface antigens (CMRF-44 and CD83) with relatively restricted expression on human DC have been described to date. We describe a third mAb, CMRF-56, which recognizes another DC early activation/differentiation antigen with limited expression on other haemopoietic cell populations. Circulating blood leukocytes did not express the CMRF-56 antigen and, following either in vitro culture or activation of PBMC populations, CMRF-56 antigen expression was detected only on DC and a subpopulation of CD19+ lymphocytes. Circulating blood DC were CMRF-56 but induced expression within 6 h of in vitro culture. This, together with the finding that tonsil and synovial fluid DC upregulate the antigen following short-term in vitro culture, confirmed that CMRF-56 recognizes an early activation antigen on DC. Isolated Langerhan's cells, dermal DC, migratory dermal DC and monocyte derived DC (GM-CSF/IL-4/TNFalpha) also express the CMIRF-56 antigen. Antigen modulation studies demonstrated that the amount of cell surface bound CMRF-56 and CMRF-44 (but not CD83) mAb was dramatically reduced by short-term incubation at 37 degrees C. This effect was not due to internalization and the reduction in CMRF-56 binding was a reversible, temperature-dependent process. In contrast, the decrease in CMRF-44 binding was irreversible, suggesting that following ligation the CMRF-44 antigen undergoes an irreversible conformational change or shedding at 37 degrees C. Western blotting confirmed that CMRF-56 recognizes a previously undescribed 95 kDa activation antigen whose cellular distribution and expression kinetics overlaps with, but is clearly distinguishable from, that of the CD83 and CMRF-44 antigens. CMRF-56 therefore provides a useful additional marker for studies on human DC.