Comparison of the anti-laminin antibody response in patients with systemic lupus erythematosus (SLE) and parasitic diseases (filariasis).

In this study, we analyzed the presence of antibodies against the basement membrane antigen laminin (LMN) in patients with systemic lupus erythematosus (SLE), filariasis, and normal controls. By ELISA, 13.8% of SLE (12/87), 66.7% of parasitized patients (20/30), and two of the normal controls had these antibodies. IgG1 anti-LMN response was elevated in all groups, whereas IgG2 and IgG3 were also elevated in parasitized patients. The analysis of the IgG anti-laminin binding capacity in SLE and parasitized patients showed similar average antibody affinity. These antibodies did not react with fibronectin by a competition ELISA. By Western blot, the anti-laminin antibodies could be demonstrated in parasitized patient sera but not in SLE sera. Moreover, the ability of these antibodies to bind to heat-treated LMN (100 degrees C for 4 min) was different. The study of the binding capacity with native or denatured LMN by Western blot and dot-blot assays showed that the anti-LMN antibodies from parasitized patients were able to react with both native and denatured forms of LMN, whereas in SLE patients these antibodies were demonstrated only with native LMN. On the other hand, the reactivity detected in the normal control sera seems to be different from the anti-LMN antibodies from SLE and parasitized patients, and probably reflects the existence of natural antibodies in these sera. The presence of anti-LMN antibodies correlates significantly with the ability of inhibition of U937 cell adhesion to LMN-coated surfaces (P < 0.0025). The difference of anti-laminin reactivity suggests that antibodies produced following immunization with autoantigens or similar molecules present in parasites have different specificities from those spontaneously produced by individuals with autoimmune diseases.

Very late activation antigen on synovial fluid T cells from patients with rheumatoid arthritis and other rheumatic diseases.

We used flow cytometry and immunoprecipitation techniques to study the expression of the activation molecules transferrin receptor, interleukin-2 receptor, HLA-DR, and very late activation antigen 1 (VLA-1) on purified T lymphocytes from peripheral blood and synovial fluid of 9 patients with rheumatoid arthritis and 7 patients with other rheumatic diseases. We found a T cell subset bearing VLA-1 in synovial fluid from 8 rheumatoid arthritis patients and 4 patients with other rheumatic diseases. VLA-1 was not found in peripheral blood T lymphocytes from either group.

Different functional domains on the transferrin receptor molecule defined by monoclonal antibodies.

Three monoclonal antibodies (mAb) FG 1/5, FG 1/6 and FG 2/12, specific for the human transferrin receptor molecule (TR), have been used to define epitopes on the TR molecule and to block natural killer lysis. FG 2/12 mAb but not FG 1/5 or FG 1/6 blocked [125I-] transferrin binding to the cellular receptor. Furthermore, FG 1/5 and FG 1/6 mAbs competed out the binding of each other to the cells but not significantly that of FG 2/12. As expected, the binding of F2/12 but not of FG 1/5 or FG 1/6 was inhibited by transferrin. In addition, FG 2/12 inhibited in a dose-dependent manner the NK activity of purified T3- large granular lymphocyte effector cells against HeLa or Molt-4 cells but not against K-562 or U937 cells. FG 1/5 preferentially inhibited NK activity against HeLa cells and FG 1/6 mAb was completely uneffective. These inhibitions were stronger at low effector to target cell (E:T) ratios than at high E:T ratios, suggesting that NK cells and anti-TR mAbs compete for the same site in the target cell. It was shown that FG 1/5 and FG 2/12 mAbs blocked cells' conjugate formation by acting at the target cell level. Our results confirm the role of TR as a one of the target structures in NK lysis and suggest that the epitope recognized by NK cells is close to but different from the transferrin binding site.

In vitro activation of cellular immune response to Gross virus-induced lymphoma.

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37 degrees C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37 degrees C but not at 4 degrees C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.