Abstract
Regulatory T cells (Tregs) are an important component of the immune system involved in regulation of immune cell proliferation and inflammatory responses and preventing autoimmune diseases. The use of Tregs in cellular therapy has recently been explored in clinical trials specifically evaluating the role of ex vivo expanded Tregs in the prevention of graft-versus-host disease during stem cell transplantation. The possibility of Treg use in the clinic requires clinical grade expansion of Tregs for development of cell therapy protocols and proper homing of Tregs to the intended target. Here we demonstrate a novel medium composition to expand CB Tregs, specifically upregulation the homing and activation markers CD62L and cutaneous lymphocyte antigen (CLA). CLA expression was uniquely acquired during activation of Tregs with subsequent loss or lack of expression with media change. This finding highlights the importance of proper growth conditions unique to Tregs that can alter expression of proteins and establishes a baseline for expanding marker specific Tregs that home and target unique tissues.
Highlights
Regulatory T cells (Tregs) are a naturally occurring subset of T cells that regulate many processes including immune homeostasis, prevention of inflammation during pathogenic exposure and inhibiting autoimmune development
We tested whether SCGM, another good manufacturing practice (GMP) medium typically used for Hematopoietic Progenitor Cells (HPC), Natural killer cells (NK) and Cytokine induced killer cells (CIK) expansion, could significantly expand cord blood (CB) Tregs (Figure 1)
While Tregs have been shown to be involved in promoting disease, uncontrolled T cell proliferation and subsequent inflammation contribute to many different diseases, of which Tregs could be useful in cellular therapy treatments
Summary
Regulatory T cells (Tregs) are a naturally occurring subset of T cells that regulate many processes including immune homeostasis, prevention of inflammation during pathogenic exposure and inhibiting autoimmune development. In all disease states, uncontrolled conventional T cells (Tcon) proliferation leads to the primary mechanisms of subsequent disease. Immunotherapy strategies have been widely used to regulate the immune system by either preventing proliferation or enhancing immune signals that may be inactivated in the patient. While the use of Tregs for immunotherapy had been previously suggested, technical aspects regarding proper source, isolation and expansion have limited practicality. Initial identification and subsequent expansion studies were done with peripheral blood (PB) Tregs due to convenient access [1, 2]. The safety and access to umbilical cord blood (CB) has provided an alternative source for Tregs and while success in expansion [3] and clinical efficacy [4, 5] has been reported, CB Treg function and phenotype is not well defined. Since isolation numbers and expansion is dramatically lower using CB, improving and optimizing expansion protocols of CB Tregs could overcome the difference in total expansion number achieved with ex vivo culture of PB Tregs
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