Anti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells
Alagesan, Senthilkumar Sanz‐Nogués, Clara Chen, Xizhe Creane, Michael Ritter, Thomas Ceredig, Rhodri O'Brien, Timothy Griffin, Matthew D.
Alagesan, Senthilkumar
Sanz‐Nogués, Clara
Chen, Xizhe
Creane, Michael
Ritter, Thomas
Ceredig, Rhodri
O'Brien, Timothy
Griffin, Matthew D.
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Publication Date
2018-02-15
Type
Article
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Citation
Alagesan, Senthilkumar, Sanz-Nogués, Clara, Chen, Xizhe, Creane, Michael, Ritter, Thomas, Ceredig, Rhodri, O'Brien, Timothy, Griffin, Matthew D. (2018). Anti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells. Immunology & Cell Biology, 96(5), 536-548. doi: doi:10.1111/imcb.12024
Abstract
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice 2 weeks after single or repeated IM injections of fully mismatched-MHC allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline. In mice subjected to hind limb ischemia (HLI), anti-donor IgG was analyzed following IM allo-MSC injection with and without administration of the T-cell immunosuppressant tacrolimus. Recipients of single and repeated IM allo-MSC developed readily-detectable anti-donor IgG. Serum anti-donor IgG levels were similar to those of allo-splenocyte recipients but had higher IgG1/IgG2a ratio and variable capacity for complement-mediated lysis of donor cells. The induced anti-donor IgG bound readily to allo-MSC and this binding was increased following allo-MSC pretreatment with interferon gamma. In mice with HLI, IM injection of allo-MSC into the ischemic limb was also associated with induction of anti-donor IgG but this was abrogated by tacrolimus (FK-506). The results indicate that allo-MSC are inherently immunogenic when delivered intramuscularly to healthy and ischemic mouse hind limb, but induce an IgG1-skewed humoral response that is suppressed by tacrolimus.
Publisher
Wiley
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Attribution-NonCommercial-NoDerivs 3.0 Ireland