The effect of alpha 1 antitrypsin on the proliferative response of human peripheral blood lymphocytes.
In evaluating immune aberrations in patients with alpha 1 antitrypsin (alpha 1 AT) deficiency, we have previously shown that they exhibit enhanced lymphocyte responsiveness to PHA that is serum mediated. In this study, we demonstrate suppression of the PHA response by using purified alpha 1 AT, and also similar but less marked suppression of the Con A response. alpha 1 AT, however, has no effect whatsoever on PWM-induced proliferation. This effect is demonstrable provided alpha 1 AT is added within 4 hr of mitogen activation and is mediated by its action on adherent cells rather than on proliferating lymphocytes. Adherent cells still exhibit this effect if pulsed with alpha 1 AT, then thoroughly washed before their activation. This suggests that it may be inhibiting a membrane serine esterase already activated before the addition of PHA. Thus alpha 1 AT may modulate the activation of T cells through its effect on monocytes, leading to abnormalities in immunoregulation, and hence a predisposition to the development of a variety of immunologic disorders in alpha 1 AT-deficient subjects.
D000328:Adult; D002448:Cell Adhesion; D003208:Concanavalin A / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D014176:Protein Biosynthesis; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D010835:Phytohemagglutinins; D000515:alpha 1-Antitrypsin; D003208:Concanavalin A