T cell receptor repertoires after adoptive transfer of expanded allogeneic regulatory T cells

Abstract

Regulatory T cell (T_reg ) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GVHD). However, our knowledge on the in-vivo persistence of transfused T_reg is limited. Whether T_reg transfusion leads to notable changes in the overall T_reg repertoire or whether longevity of T_reg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCR-α-NGS) to monitor changes in the repertoire of T_reg upon polyclonal expansion and after subsequent adoptive transfer. We applied TCR-α-NGS to samples from two patients with chronic GVHD who received comparable doses of stem cell donor derived expanded T_reg . We found that in-vitro polyclonal expansion led to notable repertoire changes in vitro and that T_reg cell therapy altered the peripheral T_reg repertoire considerably towards that of the infused cell product, to different degrees, in each patient. Clonal changes in the peripheral blood were transient and correlated well with the clinical parameters. We suggest that T cell clonotype analyses using TCR sequencing should be considered as a means to monitor longevity and fate of adoptively transferred T cells.

Keywords: T cell receptor repertoire; cell tracking; next generation sequencing; regulatory T cell therapy.