Immunomodulation by alpha 2-macroglobulin and alpha 2-macroglobulin-proteinase complexes: the effect on the human T lymphocyte response.
Alpha 2-macroglobulin (alpha 2M), various alpha 2M-proteinase complexes and methylamine-treated alpha 2M were added to human lymphocyte cultures stimulated with the specific antigen purified protein derivative of tuberculin (PPD), pokeweed mitogen (PWM) and anti-CD3. alpha 2M-trypsin diminished all reactions in a dose-dependent way. In the PPD-induced stimulation of peripheral blood mononuclear cells, both change of configuration and remaining proteinase activity contributed to the suppressive activity. Separate exposure of adherent cells or the highly purified T lymphocytes to alpha 2M-trypsin complexes indicated that the effect was mediated through adherent cells. Addition of indomethacin did not modify the results. In the interleukin 2 (IL2)-dependent stimulation of purified T lymphocytes by anti-CD3 the effect of alpha 2M-proteinase complexes was probably due to the digestion of IL 2 through remaining proteinase activity. As alpha 2M-proteinase complexes are formed at sites of inflammation, the multiple immunomodulatory effects of alpha 2M-proteinase complexes might contribute to the dysregulation of the immune system in inflammatory diseases.
Heumann
D
D
Department of Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Vischer
T L
TL
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002478:Cells, Cultured; D003864:Depression, Chemical; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D014373:Tuberculin / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000008:administration & dosage / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011043:Pokeweed Mitogens; D011948:Receptors, Antigen, T-Cell; D014373:Tuberculin; D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases