CTLA-4.FasL inhibits allogeneic responses in vivo.
Publication/Presentation Date
2-1-2006
Abstract
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 his(6)CTLA-4.FasL, effectively inhibits murine MLR. Moving in vivo, we demonstrated that subcutaneously administered his(6)CTLA-4.FasL modulates the in vivo response of infused allogeneic splenocytes. his(6)CTLA-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.
Volume
239
Issue
2
First Page
129
Last Page
135
ISSN
0008-8749
Published In/Presented At
Dranitzki-Elhalel, M., Huang, J. H., Rachmilewitz, J., Pappo, O., Parnas, M., Schmidt, W., & Tykocinski, M. L. (2006). CTLA-4.FasL inhibits allogeneic responses in vivo. Cellular immunology, 239(2), 129–135. https://doi.org/10.1016/j.cellimm.2006.05.002
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
16828466
Department(s)
Administration and Leadership
Document Type
Article