Modification of lymphocyte DNA synthesis by alpha 1-antitrypsin

Purified human alpha 1-antitrypsin (alpha 1-AT) was shown to inhibit 3H-thymidine incorporation into mouse or human lymphocytes stimulated by various mitogens or by allogeneic cells. In the mouse, both B- and T-cell responses were affected. In the human, proliferative responses of peripheral blood lymphocytes, thymocytes and T-enriched tonsillar lymphocytes to phytohaemagglutinin were inhibited as well as that of tonsillar lymphocytes to Salmonella typhi-murium lipopolysaccharide. Spontaneous 3H-thymidine incorporation was moderately and inconstantly decreased, without evidence of altered cell viability. The inhibitory effect of alpha 1-AT appears to be related to its protease inhibitory capacity. These data bring further evidence for the role of proteolytic enzymes in the early events of lymphocyte activation, and support the hypothesis that serum inhibitors of proteases may contribute to the modulation of the immune response.