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

International Immunology
M H NissenM H Claësson

Abstract

We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development of allospecific cytotoxic activity, and changed the endogenous production 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.

Citations

Nov 5, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·A E PedersenM H Claesson
Nov 1, 2006·Allergy·P K Smith, J I Harper
Oct 5, 2001·Expert Opinion on Pharmacotherapy·M Kirschfink, T E Mollnes
Apr 4, 2021·International Journal of Molecular Sciences·Matthias A FanteKathrin Renner
Apr 29, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Laura CacciaguerraMassimo Filippi

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