Figueroa Tentori, D.; (2010) Third party approach using cord blood Tregs in allo-transplantation. Doctoral thesis , UCL (University College London).

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Abstract

Compelling data has demonstrated the fundamental role of regulatory T cells (Tregs) in immuno-regulation. In vivo animal models indicate that recipient’s CD4pos CD25pos T cells adoptively transferred can prevent or control graft versus host disease (GvHD) and allograft rejection. Furthermore, it has been demonstrated that CD4pos CD25pos T cells from a third party could also be used as an adoptive cell therapy to ameliorate allo-responses. Compelling data supports that CD45RApos Tregs represent the most homogenous population among the overall Treg pool. The objective of this study is to test the "Third party approach" using CB Tregs to suppress alloresponses. Herein is shown that CB Tregs were mainly CD45RApos CD31pos (>80%), which specifically depicts RTE cells that confer a wide TCR repertoire. This study shows an optimized one-step isolation method using anti-CD25 microbeads that achieves high purity (90%) for CD4pos CD25high CD127low T cells and decreases substantially the level of effector T cells (<9% of CD4pos CD127high). Due to the low frequency of Tregs (1% from overall lymphocytes), the modality of pooling mismatch CB units for Tregs isolation was tested. The pooled CB Tregs showed constitutively potent suppression ability in vitro. Interestingly, in 40% of the cases a better suppression was seen with pCB Tregs compared to individual CB Tregs suggesting a “synergetic effect”. In summary, this study suggests that CB units fulfill the optimal properties for the isolation of bona fide Tregs, which can be isolated with the highest purity using a single step isolation method under GMP standards. Moreover, this study suggests that CB Tregs can be intentionally pooled and tailored under the required HLA matches for clinical settings.

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