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- Title
Antigen‐specific CD4<sup>+</sup>CD25<sup>+</sup> T cells induced by locally expressed ICOS‐Ig: the role of Foxp3, Perforin, Granzyme B and IL‐10 ‐ an experimental study.
- Authors
Christiansen, Dale; Mouhtouris, Effie; Hodgson, Russell; Sutton, Vivien R.; Trapani, Joseph A.; Ierino, Francesco L.; Sandrin, Mauro S.
- Abstract
Summary: We have previously reported that ICOS‐Ig expressed locally by a PIEC xenograft induces a perigraft cellular accumulation of CD4+CD25+Foxp3+ T cells and specific xenograft prolongation. In the present study we isolated and purified CD4+CD25+ T cells from ICOS‐Ig secreting PIEC grafts to examine their phenotype and mechanism of xenograft survival using knockout and mutant mice. CD4+CD25+ T cells isolated from xenografts secreting ICOS‐Ig were analysed by flow cytometry and gene expression by real‐time PCR. Regulatory function was examined by suppression of xenogeneic or allogeneic primed CD4 T cells in vivo. Graft prolongation was shown to be dependent on a pre‐existing Foxp3+ Treg, IL‐10, perforin and granzyme B. CD4+CD25+Foxp3+ T cells isolated from xenografts secreting ICOS‐Ig demonstrated a phenotype consistent with nTreg but with a higher expression of CD275 (ICOSL), expression of CD278 (ICOS) and MHC II and loss of CD73. Moreover, these cells were functional and specifically suppressed xenogeinic but not allogeneic primed T cells in vivo.
- Subjects
T cells; GENE flow; KNOCKOUT mice; GENE expression; FLOW cytometry; CYTOTOXIC T cells; GRAFT versus host reaction
- Publication
Transplant International, 2019, Vol 32, Issue 11, p1203
- ISSN
0934-0874
- Publication type
Article
- DOI
10.1111/tri.13474