C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

We have previously shown that activated C1s complement and activated Tcells cleave beta2-microglobulin (beta2m) in vitro leading to the formationof desLys58 beta2m. This process can specifically be inhibited byC1-esterase inhibitor (C1-inh). Furthermore we showed that exogenouslyadded desLys58 beta2m in nanomolar amounts to a one-way allogenic mixedlymphocyte culture (MLC) increased the endogenous production of IL-2 andthe generation of allo-specific cytotoxic T lymphocytes. C1-inh waspurified from fresh human plasma and added to human or murine MLC andmitogen-stimulated lymphocyte cultures grown in the presence ofcomplement-inactivated serum. Read-outs were cell proliferation, lymphokineproduction and development of T cell-mediated cytotoxicity. We found thataddition of C1-inh to MLC and mitogen- exposed murine and human lymphocytecultures inhibited proliferation, the development of allospecific cytotoxicactivity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12and IFN-gamma. These data clearly demonstrate a regulatory function ofC1-inh on T cell- mediated immune functions.