C1-ESTERASE INHIBITOR BLOCKS T-LYMPHOCYTE PROLIFERATION AND CYTOTOXICT-LYMPHOCYTE GENERATION IN-VITRO

We have previously shown that activated Cls complement and activated T cells cleave beta(2)-microglobulin (beta(2)m) in vitro leading to the formation of desLys(58)beta(2)m. This process can specifically be inh ibited by C1-esterase inhibitor (C1-inh), Furthermore we showed that e xogenously added desLys(58)beta(2)m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous prod uction of IL-2 and the generation of allo-specific cytotoxic T lymphoc ytes. C1-inh was purified from fresh human plasma and added to human o r murine MLC and mitogen-stimulated lymphocyte cultures grown in the p resence of complement-inactivated serum, Read-outs were cell prolifera tion, lymphokine production and development of T cell-mediated cytotox icity. We found that addition of C1-inh to MLC and mitogen-exposed mur ine and human lymphocyte cultures inhibited proliferation, the develop ment of allospecific cytotoxic activity, and changed the endogenous pr oduction of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions.