INHIBITION OF ACTIVATION OF HUMAN T-LYMPHOCYTES BY THE COMPLEMENT C1 ESTERASE INHIBITOR

The major histocompatibility complex (MHC) class I molecules have been shown to be substrates to both of the complement C1 esterases. The ef fect of a C1 esterase-mediated cleavage of the MHC class I molecules o n the activation process of lymphocytes was investigated by including the complement C1 esterase inhibitor (C1-Inh) in the medium during act ivation of human peripheral lymphocytes by staphylococcal enterotoxin A (SEA). The C1-Inh was shown to inhibit the activation of both CD4(+) and CD8(+) cells. No effect on activation of B lymphocytes was record ed, although the complement C1 complex was shown to bind to the B lymp hocytes. Furthermore, the C1 complex bound to mononuclear cells was sh own to be cleaved into molecular weights corresponding to the activate d forms of the C1 esterases. The effect of the C1-Inh was much more pr onounced at low cell density and the inhibition was not affected by th e addition of interleukin-2 (IL-2). However, the inhibition was reduce d when the cells were disturbed by addition of new portions of Cl-Inh, 24 and 48 hr after the initiation of the activation. This indicates t hat the C1-Inh interference with the activation of T lymphocytes is me diated through a mechanism that requires some form of cell contact.