CD40·FasL inhibits human T cells: Evidence for an auto-inhibitory loop-back mechanism

M. Dranitzki-Elhalel*, J. H. Huang, M. Sasson, J. Rachmilewitz, M. Parnas, M. L. Tykocinski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


A chimeric CD40·FasL (CD40-CD95L) 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). CD40·FasL, 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) CD40·FasL is cytotoxic to Fas receptor-positive cell lines of different cell lineages, (ii) CD40·FasL's function is potentiated when there is enforced expression of CD40L on target cells, (iii) CD40·FasL 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 CD40·FasL 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.

Original languageAmerican English
Pages (from-to)355-363
Number of pages9
JournalInternational Immunology
Issue number4
StatePublished - Apr 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant AI31044-11 (M.L.T.), and by the Israeli Society of Nephrology research fund for 2003 (M.D.E.).


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