CTLA-4·FasL inhibits allogeneic responses in vivo

M. Dranitzki-Elhalel*, J. H. Huang, J. Rachmilewitz, O. Pappo, M. Parnas, W. Schmidt, M. L. Tykocinski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


CTLA-4·Fas ligand (CTLA-4·FasL), a paradigmatic 'trans signal converter protein (TSCP)', can attach to APC (via CTLA-4 binding to B7) and direct intercellular inhibitory signals to responding T cells (via FasL binding to Fas receptor), converting an activating APC-to-T cell signal into an inhibitory one. Our previous studies established that CTLA-4·FasL inhibits human primary mixed lymphocyte reactions (MLR) and induces alloantigen-specific hyporesponsiveness ex vivo. The present study extends this to an in vivo context. Using splenocytes from MHC-mismatched C57BL/6 and Balb/c mice, we demonstrated that his6CTLA-4·FasL, effectively inhibits murine MLR. Moving in vivo, we demonstrated that subcutaneously administered his6CTLA-4·FasL modulates the in vivo response of infused allogeneic splenocytes. his6CTLA-4·FasL reduces the number of cells in each cell division, and increases the percentage of dead cells in each division. These findings are consistent with an antigen-induced cell death of the alloreactive cells, and bolsters recombinant TCSP promise as a therapeutic for transplantation diseases.

Original languageAmerican English
Pages (from-to)129-135
Number of pages7
JournalCellular Immunology
Issue number2
StatePublished - Feb 2006
Externally publishedYes

Bibliographical note

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


  • Activation-induced cell death (AICD)
  • CD4 T cells
  • CD8 T cells
  • In vivo mixed lymphocyte reaction
  • Inhibition of alloresponse
  • Trans signal converter protein (TSCP)


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