Dendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival

Francesco L Ierino, William Mulley, Natalie Dodge, Yu Qin Li, Effie Mouhtouris, Dale Christiansen, Mauro Sergio Sandrin

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Dendritic cells (DCs) and CTLA4Ig are important in regulating T-cell responses and therefore represent potential therapeutic tools in transplantation. In this study, CTLA4Ig was expressed in a C57BL/6 murine DC line (JAWS II) by lentiviral transduction and these cells were used to examine T-cell immunomodulatory effects in vitro and in vivo. A lower stimulation index to C57BL/6 was observed with splenocytes from BALB/c mice primed with JAWS II-CTLA4Ig compared with control JAWS II-green fluorescent protein (JAWS II-GFP). Mice primed with JAWS II-CTLA4Ig cells had significantly prolonged antigen-specific C57BL/6 skin graft survival compared with either JAWS II-GFP-primed or naïve mice (median 13, 11 and 11 days, respectively, P=0.0001). Furthermore, JAWS II-CTLA4Ig-primed mice that had been previously transplanted with skin grafts were re-transplanted with skin grafts 6 months later without immune manipulation. These mice demonstrated specific prolongation of second-set rejection responses, indicating systemic immune modulation induced by genetically modified DC. The mechanism was not due to expression of indoleamine 2,3-dioxygenase or induction of circulating regulatory T cells as assessed by flow cytometry of the peripheral blood lymphocytes. This potent effect demonstrated with skin grafts and second-set responses highlights the potential use of this strategy for transplantation more generally.

Original languageEnglish
Pages (from-to)846-850
Number of pages5
JournalImmunology and Cell Biology
Volume88
Issue number8
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

Keywords

  • CTLA-4Ig
  • DCs
  • skin graft

Cite this

Ierino, F. L., Mulley, W., Dodge, N., Li, Y. Q., Mouhtouris, E., Christiansen, D., & Sandrin, M. S. (2010). Dendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival. Immunology and Cell Biology, 88(8), 846-850. https://doi.org/10.1038/icb.2010.58
Ierino, Francesco L ; Mulley, William ; Dodge, Natalie ; Li, Yu Qin ; Mouhtouris, Effie ; Christiansen, Dale ; Sandrin, Mauro Sergio. / Dendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival. In: Immunology and Cell Biology. 2010 ; Vol. 88, No. 8. pp. 846-850.
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abstract = "Dendritic cells (DCs) and CTLA4Ig are important in regulating T-cell responses and therefore represent potential therapeutic tools in transplantation. In this study, CTLA4Ig was expressed in a C57BL/6 murine DC line (JAWS II) by lentiviral transduction and these cells were used to examine T-cell immunomodulatory effects in vitro and in vivo. A lower stimulation index to C57BL/6 was observed with splenocytes from BALB/c mice primed with JAWS II-CTLA4Ig compared with control JAWS II-green fluorescent protein (JAWS II-GFP). Mice primed with JAWS II-CTLA4Ig cells had significantly prolonged antigen-specific C57BL/6 skin graft survival compared with either JAWS II-GFP-primed or na{\"i}ve mice (median 13, 11 and 11 days, respectively, P=0.0001). Furthermore, JAWS II-CTLA4Ig-primed mice that had been previously transplanted with skin grafts were re-transplanted with skin grafts 6 months later without immune manipulation. These mice demonstrated specific prolongation of second-set rejection responses, indicating systemic immune modulation induced by genetically modified DC. The mechanism was not due to expression of indoleamine 2,3-dioxygenase or induction of circulating regulatory T cells as assessed by flow cytometry of the peripheral blood lymphocytes. This potent effect demonstrated with skin grafts and second-set responses highlights the potential use of this strategy for transplantation more generally.",
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Ierino, FL, Mulley, W, Dodge, N, Li, YQ, Mouhtouris, E, Christiansen, D & Sandrin, MS 2010, 'Dendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival', Immunology and Cell Biology, vol. 88, no. 8, pp. 846-850. https://doi.org/10.1038/icb.2010.58

Dendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival. / Ierino, Francesco L; Mulley, William; Dodge, Natalie; Li, Yu Qin; Mouhtouris, Effie; Christiansen, Dale; Sandrin, Mauro Sergio.

In: Immunology and Cell Biology, Vol. 88, No. 8, 11.2010, p. 846-850.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ierino, Francesco L

AU - Mulley, William

AU - Dodge, Natalie

AU - Li, Yu Qin

AU - Mouhtouris, Effie

AU - Christiansen, Dale

AU - Sandrin, Mauro Sergio

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