Immunomodulation by α2‐macroglobulin and α2‐macroglobulin‐proteinase complexes: the effect on the human T lymphocyte response

摘要

AbstractAlpha2‐macroglobulin (α2M), various α2M‐proteinase complexes and methylamine‐treated α2M were added to human lymphocyte cultures stimulated with the specific antigen purified protein derivative of tuberculin (PPD), pokeweed mitogen (PWM) and anti‐CD3. α2M‐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 α2M‐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 α2M‐proteinase complexes was probably due to the digestion of IL2 through remaining proteinase activity. As α2M‐proteinase complexes are formed at sites of inflammation, the multiple immunomodulatory effects of α2M‐proteinase complexes might contribute to the dysregulation of the immun