CD40FasL inhibits human T cells: evidence for an auto-inhibitory loop-back mechanism
Authors: Dranitzki-Elhalel, M.; Huang, J. H.; Sasson, M.; Rachmilewitz, J.; Parnas, M.; Tykocinski, M. L.
Source: International Immunology, Volume 19, Number 4, 15 April 2007 , pp. 355-363(9)
Publisher: Oxford University Press
Abstract:A chimeric CD40FasL (CD40CD95L) protein was designed with the combined capacities to bind to two surface receptors on activated T cells, CD40 ligand (CD40L; CD154) and Fas receptor (CD95). CD40FasL, once tethered to the cell surface via one of its ends, can transmit a signal via its other end. In principle, simultaneous triggering from both ends is possible, and thus there is the intriguing potential for auto-inhibition if such dual triggering occurs on the same cell itself. Several lines of evidence support this mechanism: (i) CD40FasL is cytotoxic to Fas receptor-positive cell lines of different cell lineages, (ii) CD40FasL's function is potentiated when there is enforced expression of CD40L on target cells, (iii) CD40FasL inhibition does not require intercellular contact, as demonstrated by soft agar clone formation and cell dilution analysis and (iv) introduction of exogenous CD40 into the system interferes with CD40FasL inhibition. Taken together, these data are consistent with a loop-back inhibitory mechanism within individual activated (CD40L and Fas receptor expressing) T cells causing suicide of these T cells. Significantly, this type of fusion protein provides a unique way to confine immunoinhibition to activated T cells.
Document Type: Research Article
Publication date: 2007-04-15
- International Immunology publishes a broad range of experimental and theoretical studies in molecular and cellular immunology conducted in laboratories throughout the world.