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

doi:10.1016/j.cellimm.2006.05.002

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 journal › Article › peer-review

11 Scopus citations

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 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 language	English
Pages (from-to)	129-135
Number of pages	7
Journal	Cellular Immunology
Volume	239
Issue number	2
DOIs	https://doi.org/10.1016/j.cellimm.2006.05.002
State	Published - Feb 2006
Externally published	Yes

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.).

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cellimm.2006.05.002

Cite this

@article{ca251ba9ecb34806bb17efd001f97513,

title = "CTLA-4·FasL inhibits allogeneic responses in vivo",

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 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.",

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

author = "M. Dranitzki-Elhalel and Huang, {J. H.} and J. Rachmilewitz and O. Pappo and M. Parnas and W. Schmidt and Tykocinski, {M. L.}",

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.). ",

year = "2006",

month = feb,

doi = "10.1016/j.cellimm.2006.05.002",

language = "אנגלית",

volume = "239",

pages = "129--135",

journal = "Cellular Immunology",

issn = "0008-8749",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - CTLA-4·FasL inhibits allogeneic responses in vivo

AU - Dranitzki-Elhalel, M.

AU - Huang, J. H.

AU - Rachmilewitz, J.

AU - Pappo, O.

AU - Parnas, M.

AU - Schmidt, W.

AU - Tykocinski, M. L.

N1 - 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.).

PY - 2006/2

Y1 - 2006/2

N2 - 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.

AB - 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.

KW - Activation-induced cell death (AICD)

KW - CD4 T cells

KW - CD8 T cells

KW - In vivo mixed lymphocyte reaction

KW - Inhibition of alloresponse

KW - Trans signal converter protein (TSCP)

UR - http://www.scopus.com/inward/record.url?scp=33745857279&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2006.05.002

DO - 10.1016/j.cellimm.2006.05.002

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 16828466

AN - SCOPUS:33745857279

SN - 0008-8749

VL - 239

SP - 129

EP - 135

JO - Cellular Immunology

JF - Cellular Immunology

IS - 2

ER -

CTLA-4·FasL inhibits allogeneic responses in vivo

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this