Characterization and expansion of baboon CD4⁺CD25⁺ Treg cells for potential use in a non‐human primate xenotransplantation model

Abstract

We demonstrate that baboon Treg cells suppress immune responses to xenogeneic stimulation. These studies suggest that adoptive transfer of expanded Treg cells into transplant recipients may provide an approach to prevent cell-mediated rejection of grafts and potentially induce tolerance in the pig to baboon xenotransplantation preclinical model.

Restimulation After Cryopreservation and Thawing Preserves the Phenotype and Function of Expanded Baboon Regulatory T Cells

“…Treg infusion may also play an important role in preventing rejection or promoting tolerance of transplanted solid organs (5). This is supported by in vitro data demonstrating powerful suppression of alloreactive cells using Treg in mouse (6, 7), primate (8, 9), and human (10) models as well as pig-to-primate xenogeneic models (11, 12). …”

“…The use of rapamycin also varies between protocols. All protocols remain experimental, and the only 2 previous reports of baboon ( Papio hamadryas ) Treg expansion produced approximately 200-fold expansion (11, 12). This is insufficient for a trial of pig-to-primate Treg therapy using baboons as the recipients or for clinical trials.…”

All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species

“…Recent work has documented the expression of FOXP3 by equine CD4 + T cells using cross-reactive anti-human FOXP3 (PCH101) and anti-murine Foxp3 (FJK-16s) mAbs (A.M. de Mestre, personal communication). Other species in which regulatory cells have been described include the guinea pig [375][376][377][378], baboon [379,380], macaque [381][382][383] and chimpanzee [384]. Furthermore, a recent study described the generation of IL-10 + T cells from chicken CD4 + CD25 − T cells by culturing them with anti-CD3/CD28-coated beads, IL-2 and TGF-β [385], while the anti-human FOXP3 mAb 236A/ E7 yielded positive immunohistochemical staining of the mesenteric lymph nodes of harbour seals and a walrus [386].…”

Determination of Absolute Counts of Circulating Regulatory T Cells in Cynomolgus Macaques Using an Optimized Flow Cytometric Method

“…CD127 expression is a useful marker for Treg immunophenotyping (IP) panel development because of its expression on the cell surface, and as such, it requires fewer experimental manipulations compared with intracellular FoxP3 staining. Tregs have been previously enumerated in rhesus and cynomolgus macaques and baboons, but differing assay methods have resulted in variable staining results and ranges for Tregs in these species (Law et al 2009;Porter et al 2007). To our knowledge, there is a lack of information on the range of absolute numbers of circulating Tregs in healthy, naive cynomolgus macaques, as has been previously performed for other lymphocyte subsets (Baker et al 2008;Bleavins et al 1993 …”

“…Regulatory T cells (Tregs) are a rare subset of lymphocytes that inhibit the activation and effector functions of T cells and are key players in transplantation biology (Porter et al 2007), allergies (Trzonkowski et al 2009), and autoimmune disorders (Feuerer et al 2007;Sakaguchi 2004;Sakaguchi et al 1995). Increasingly, Tregs are being investigated as possible therapeutic targets because of their critical mechanism of maintaining self-tolerance and regulating the immune response (Hori, Takahashi, et al 2003;Jung and Seoh 2009;Sakaguchi 2004).…”