Modulation of IgM anti-lymphocyte antibody-reactive T cell surface antigens in systemic lupus erythematosus.
Cold-reactive lymphocytotoxic autoantibodies are present in the serum of most patients with active systemic lupus erythematosus (SLE) and may be important for the development of the lymphopenia and T cell dysfunction characteristic of this disorder. Neither the mechanisms of autoantibody action in this regard, nor the nature of the relevant T cell membrane target molecules have been defined, however. In the present investigation, preincubation of T cells with SLE serum at 37 degrees C reduced their reactivity with SLE IgM anti-lymphocyte autoantibodies, as demonstrated by indirect immunofluorescence and complement-dependent cytotoxicity. Modulation was restricted to SLE IgM autoantibody-reactive antigen; monoclonal antibody staining of various T cell differentiation and activation antigens remained unchanged. Loss of antigen from the surface membrane was rapid, but transient. A nadir was reached after approximately 120 min of 37 degrees C incubation, followed by essentially complete reexpression of antigen several hours later. Although modulation occurred spontaneously at 37 degrees C in the absence of SLE serum, loss of antigen was enhanced by IgM anti-lymphocyte autoantibodies, despite their low thermal amplitude. Modulation was inhibited by sodium azide, by fixation of cells with paraformaldehyde, and by low incubation temperatures. Colchicine and cytochalasin D had no effect on this process, suggesting that the integrity of the cytoskeleton was not essential. Cycloheximide did not prevent loss of antigen, but inhibited its reexpression. In experiments to determine the fate of modulated antigen, both intracytoplasmic accumulation and shedding from the cell surface were demonstrated. Only shedding was increased by the presence of anti-lymphocyte antibodies, however. These studies delineate modulation of T cell membrane antigen as a new mechanism for anti-lymphocyte autoantibody action in SLE. The occurrence of modulation at physiologic temperatures in vitro suggests that a similar phenomenon of potential relevance to T cell dysfunction may obtain in patients with this disorder.
D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000502:physiology*; D001323:Autoantibodies / Q000502:physiology; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology*; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013696:Temperature; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D001613:beta 2-Microglobulin / Q000276:immunology
D000954:Antigens, Surface; D000961:Antilymphocyte Serum; D001323:Autoantibodies; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D001613:beta 2-Microglobulin