Immunogenicity of allogeneic mesenchymal stem cells.
Bottom Line: However, intravenous injection of allo-MSCs in rats led to the formation of alloantibodies with the capacity to facilitate complement-mediated lysis, although IgM levels were markedly decreased compared with animals that received T cells.The allo-MSC induced immune response was sufficient to lead to significantly reduced survival of subsequently injected allo-MSCs.Interestingly, no increased immunogenicity of IFN-γ stimulated allo-MSCs was observed in vivo.
Affiliation: College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.Show MeSH
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Mentions: Next, we analysed whether injection of allogeneic MSCs leads to the activation of T cells in vivo. First, we tested for systemic early activation of CD4+ T cells in response to allogeneic MSCs. Spleens were harvested from animals 24 or 48 hr after injection of 5 × 106 MSCs, T cells or PBS and expression of the early activation markers CD25 and CD71 as well as expression of CD62L on CD4+ T cells was analysed by flow cytometry (Fig. 3). We found that in allo-T cell-injected animals, more CD4+CD25+CD71+ and CD4+CD62L− cells were detectable at 24 and 48 hr compared to PBS and allo-MSC-injected rats. Levels of T cell activation were similar in allo-MSC-treated and control-treated rats at both time points. In addition to the characterization of T cell activation in the spleen, T cells from mesenteric lymph nodes were also analysed for the expression of pro-inflammatory cytokines upon injection of allo-MSCs. The relative quantities of IL-1β, IL-2, IL-6 and IFN-γ mRNAs compared with β-actin mRNA were analysed with TaqMan semi-quantitative real time PCR (Invitrogen). No significant changes in the mRNA expression profile of any of these immune markers could be detected in lymphocytes of allo-MSC-injected animals after 24 and 48 hr when compared to PBS controls (Fig. S1). In contrast, injection of allogeneic T cells led to a transient upregulation of mRNAs of all inflammatory cytokines investigated after 24 hr.
Affiliation: College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.