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.

Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre‐ and post‐transplantation cytokine responses in stimulated whole blood

“…As some events occurred in the same patient, the total number of patients who had experienced an inflammatory event (infection/acute GvHD) before post-HCT whole blood sampling was 10 (33%). At the day of post-HCT whole blood sampling, these 10 patients had higher levels of C-reactive protein (median [Q1-Q3] 11 mg/L vs. 3 [1][2][3][4][5][6][7][8] mg/L in patients without a prior inflammatory event).…”

“…Following conditioning, almost all patients experience pancytopenia for a period of days to weeks depending on the intensity of the regimen and the source of the infused allograft (peripheral blood, bone marrow or umbilical cord blood). Neutrophils, dendritic cells and monocytes are the first circulating immune cells to recover to normal levels, typically within 2‐3 weeks after HCT, followed by NK‐cells within 1‐3 months after HCT and CD8+ T cells, B cells and finally CD4+ T cells within several months to years after HCT 2‐4 . However, despite the quantitative reconstitution of the different immune cells, HCT recipients remain immunocompromised, and infections are a major cause of transplant‐related mortality both early and late after transplantation 5 …”

“…Neutrophils, dendritic cells and monocytes are the first circulating immune cells to recover to normal levels, typically within 2-3 weeks after HCT, followed by NK-cells within 1-3 months after HCT and CD8+ T cells, B cells and finally CD4+ T cells within several months to years after HCT. [2][3][4] However, despite the quantitative reconstitution of the different immune cells, HCT recipients remain immunocompromised, and infections are a major cause of transplant-related mortality both early and late after transplantation. 5 A potential strategy to reduce the incidence of post-HCT infections is to tailor antimicrobial prophylaxis not only according to the quantitative measures of immune cell reconstitution but also according to the functional immune reconstitution.…”

T Cell Subsets During Early Life and Their Implication in the Treatment of Childhood Acute Lymphoblastic Leukemia

“…However, the current picture of post-HSCT dynamics is that Tregs are normalized within weeks followed by the recovery of memory CD4 + and CD8 + T cell within months. In contrast, the recovery of naïve T cell pool can take years, likely as this population relies on thymic output and not on peripheral homeostasis and expansion ( 76 ). Finally, while chemotherapy and HSCT have been shown to clearly impact the proportions of circulating T cells, there are almost no studies that systematically assess the functional responses of T cells (in particular the memory population) following ALL treatment.…”

Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust

“…The increased immune suppressive environment after PTCy would also better explain the conflicting data reported on numbers between different immune reconstitution patterns observed after ATG and PTCy-based transplantation regimens. 33 , 75 The described substantial differences in immune reconstitution patterns depending on transplantation regimens most likely explain the aforementioned conflicting data on the impact of CMV reactivation on leukemia control. NK and γδT cells, particularly after αβT cell depletion, are dominant subsets that will be protective as they both expand upon CMV reactivation and also cross-react with leukemic cells.…”