Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein

Esma S. Yolcu, Xiao Gu, Chantale Lacelle, Hong Zhao, Laura Bandura-Morgan, Nadir Askenasy, Haval Shirwan

Research output: Contribution to journalArticle

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Abstract

The critical role played by Fas ligand (FasL) in immune homeostasis renders this molecule an attractive target for immunomodulation to achieve tolerance to auto- and transplantation Ags. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging. Therefore, we tested the efficacy of donor splenocytes rapidly and efficiently engineered to display on their surface a chimeric form of FasL protein (SA-FasL) for tolerance induction to cardiac allografts. The i.p. injection of ACI rats with Wistar-Furth rat splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third-party cardiac allografts. Tolerance was associated with apoptosis of donor reactive T effector cells and induction/expansion of CD4 +CD25+FoxP3+ T regulatory (Treg) cells. Treg cells played a critical role in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naive unmanipulated ACI rats resulted in indefinite survival of secondary Wistar-Furth grafts. Immunomodulation with allogeneic cells rapidly and efficiently engineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapy with potential application to regenerative medicine, transplantation, and autoimmunity.

Original languageEnglish (US)
Pages (from-to)931-939
Number of pages9
JournalJournal of Immunology
Volume181
Issue number2
StatePublished - Jul 15 2008

Fingerprint

Fas Ligand Protein
Allografts
Immunomodulation
Regulatory T-Lymphocytes
Inbred ACI Rats
Transplantation
Inbred WF Rats
Transplants
Regenerative Medicine
Isoantigens
Adoptive Transfer
Cell- and Tissue-Based Therapy
Autoimmunity
Homeostasis
Apoptosis
Injections

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein. / Yolcu, Esma S.; Gu, Xiao; Lacelle, Chantale; Zhao, Hong; Bandura-Morgan, Laura; Askenasy, Nadir; Shirwan, Haval.

In: Journal of Immunology, Vol. 181, No. 2, 15.07.2008, p. 931-939.

Research output: Contribution to journalArticle

Yolcu, Esma S. ; Gu, Xiao ; Lacelle, Chantale ; Zhao, Hong ; Bandura-Morgan, Laura ; Askenasy, Nadir ; Shirwan, Haval. / Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein. In: Journal of Immunology. 2008 ; Vol. 181, No. 2. pp. 931-939.
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