Abstract
Allogeneic hematopoietic cell transplantation (HCT) is a powerful therapy to treat multiple hematological diseases. The intensive conditioning regimens used to allow for donor hematopoietic stem cell (HSC) engraftment are often associated with severe toxicity, delayed immune reconstitution, life-threatening infections, and thus higher relapse rates. Additionally, due to the high incidence of graft versus host disease (GvHD), HCT protocols have evolved to prevent such disease that has a detrimental impact on antitumor and antiviral responses. Here, we analyzed the role of host T and natural killer (NK) cells in the rejection of donor HSC engraftment as well as the impact of donor regulatory T cells (Treg) and NK cells on HSC engraftment. We review some of the current strategies that utilize NK or Treg to improve allogeneic HCT therapy in order to accomplish better HSC engraftment and immune reconstitution and achieve a lower incidence of cancer relapse, opportunistic infections, and GvHD.
Highlights
Hematopoietic cell transplantation (HCT) is the only curative treatment for high-risk leukemias and lymphomas and for several nonmalignant hematologic diseases such as hemoglobinopathies and severe combined immune deficiencies
After total lymphoid irradiation (TLI)/antithymocyte globulin (ATG) treatment, the residual T cell pool is highly enriched in Treg and preclinical studies showed that in the TLI/ATG setting host-type Treg together with invariant natural killer T cells play a crucial role in protecting donor cells from host immune attack permitting the development of stable mixed chimerism and inducing tolerance to organ transplantation [104]
We recently reported that the administration of low doses of invariant natural killer T cells (iNKT) expands donor Treg in vivo in HCT models allowing for effective graft versus host disease (GvHD) prevention [118]
Summary
Hematopoietic cell transplantation (HCT) is the only curative treatment for high-risk leukemias and lymphomas and for several nonmalignant hematologic diseases such as hemoglobinopathies and severe combined immune deficiencies. The infusion of a “megadose” of stem cells from the donor and their “veto” effect coupled with depletion of residual radio- and chemoresistant host T cells in vivo allowed for successful HSC engraftment even in these challenging clinical situations [11,12,13,14]. Despite these clinical advancements and strategies that made HCT available to most of the patients that required it, they have still resulted in a number of significant complications [15]. Treg have been widely studied for their tolerogenic properties and their ability to suppress conventional T cells (Tcon) and other immune cells such as NK and B cells in vitro and in vivo; they hold tremendous promise for clinical application in the HCT setting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
