Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

Abstract

Allogeneic (allo) hematopoietic cell transplantation (HCT) is the only curative treatment option for patients suffering from chemotherapy-refractory or relapsed hematological malignancies. The occurrence of morbidity and mortality after allo-HCT is still high. This is partly correlated with the immunological recovery of the T cell subsets, of which the dynamics and relations to complications are still poorly understood. Detailed information on T cell subset recovery is crucial to provide tools for better prediction and modulation of adverse events. Here, we review the current knowledge regarding CD4⁺ and CD8⁺ T cells, γδ T cells, iNKT cells, Treg cells, MAIT cells and naive and memory T cell reconstitution, as well as their relations to outcome, considering different cell sources and immunosuppressive therapies. We conclude that the T cell subsets reconstitute in different ways and are associated with distinct adverse and beneficial events; however, adequate reconstitution of all the subsets is associated with better overall survival. Although the exact mechanisms involved in the reconstitution of each T cell subset and their associations with allo-HCT outcome need to be further elucidated, the data and suggestions presented here point towards the development of individualized approaches to improve their reconstitution. This includes the modulation of immunotherapeutic interventions based on more detailed immune monitoring, aiming to improve overall survival changes.

Keywords: T cell subsets; allogeneic hematopoietic cell transplantation; biomarkers; conditioning; hematological malignancies; immune reconstitution; immunosuppressive therapies; serotherapy.

Figure 1

Schematic overview of the reconstitution of the distinct T cell subsets following allogeneic hematopoietic cell transplantation (HCT). iNKT, γδ T cells and Treg cells rapidly recover within weeks to normal levels after the time of Transplant. CD8⁺, CD4⁺ and memory T cell recovery can be as early as one to two months, and these subsets subsequently reconstitute within one to two years. Reconstitution of the naive T cell pool highly depends on thymopoiesis and can take years, starting around three months after transplantation. MAIT cell frequencies seem to remain extremely low within the first year and only reach normal levels after years following allogeneic HCT.

Figure 2

Overview of T cell subset related to allogeneic HCT outcomes and factors affecting T cell reconstitution before and after allo-HCT. Adequate reconstitution of the distinct T cell subsets is differently correlated to relapse, GvHD, VR and overall survival following allo-HCT. Adequate reconstitution of the T cell compartment is highly influenced by distinct factors before and after transplantation.