Immune Reconstitution Following Hematopoietic Cell Transplantation

Dudakov, Jarrod A; Perales, Miguel-Ángel; Brink, Marcel R.M. van den

doi:10.1002/9781118416426.ch15

Cited by 11 publications

(11 citation statements)

References 196 publications

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“…In fact, the general phenomenon of endogenous thymic regeneration has been known for longer even than its immunological function (3, 4), however, the underlying mechanisms controlling this process remain unstudied. Although there is likely continual thymic involution and regeneration in response to stress and infection in otherwise healthy people, acute and profound thymic damage such as that caused by common cancer cytoreductive therapies or the conditioning regimes as part of hematopoietic cell transplantation (HCT), leads to prolonged T cell deficiency; precipitating high morbidity and mortality from opportunistic infections and may even facilitate cancer relapse (5, 6). Furthermore, the continuous decline in thymic function with age drastically erodes the regenerative capacity of the thymus (2, 7).…”

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confidence: 99%

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

et al. 2018

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The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity.

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confidence: 99%

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

et al. 2018

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“…There are different methods to assess the immune recovery after transplant, such as estimation of absolute lymphocyte count (ALC), levels of immune cell subsets (NK cells, B cells, and T cells), and antibody titers to assays for T-and B-cell repertoires [91].…”

Section: Assessment Of Post-transplant Immune Recoverymentioning

confidence: 99%

“…Surface markers such as CD45RA, CD28, CD27, CD62L, and CCR7 can be used to differentiate naïve, effector, effector memory, and central memory CD4+ and CD8+ subsets [101,102]. The surface markers expressed by naïve T cells are CD45RA+CCR7+; central memory T cells are CD45RA-CCR7+; effector memory T cells are CD45RA-CCR7-; and effector T cells are CD45RA+CCR7- [91]. CD4+ T cells also include regulatory T cells (CD25+FoxP3+) and Th17 cells [103,104].…”

Section: Assessment Of Post-transplant Immune Recoverymentioning

confidence: 99%

Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation

Singh¹,

D’Silva²,

Saxena³

2020

Cells of the Immune System

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for both congenital and hematological malignancies. Immune reconstitution after allogeneic hematopoietic stem cell transplantation is implicated in successful transplant outcomes such as overall survival and relapse-free survival. The reconstitution of immune cell subsets after HSCT occurs in different phases at different time points encompassing pre-engraftment, engraftment, and post-engraftment. The recovery of innate cellular immunity with the appearance of monocytes, dendritic cells, and natural killer cells in peripheral blood correlates with initiation of cellular engraftment. The cellular adaptive immunity is characterized by both thymicindependent expansion of T cells infused with graft and thymus-dependent expansion of naïve T cells derived from donor stem cells. The humoral immunity consists of B-cell reconstitution, which consists primarily of transitional and naïve subsets with the recovery of memory B cells that occur much later. In this review, we highlight the factors affecting immune reconstitution, the reconstitution of innate and adaptive immunity, techniques to assess immune reconstitution, and ways to enhance it.

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“…Immune Reconstitution.-Conditioning regimens serve to destroy not only tumor cells but also immune cells, thereby depleting significantly the recipient's immune system. This profound immunosuppression helps prevent rejection of the transplanted stem cells by the host immune system and enables their engraftment in the bone marrow, 46 but also increases the risk of infection.…”

Section: Infectious Complications Of the Gastrointestinal Tractmentioning

confidence: 99%

“…The time course of immune recovery can be affected by several factors, including the degree of age-related involution of the thymus, the source of progenitor cells, the graft manipulation before infusion, the degree of HLA disparity, the conditioning regimen, and the subsequent development of GVHD. 46 Reconstitution of different immune cell subsets occurs over different periods of time. [47][48][49][50] Recovery of the innate hematopoietic cell counts occurs within weeks of HSCT.…”

Section: Infectious Complications Of the Gastrointestinal Tractmentioning

confidence: 99%

Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation

Mourad

Michel

Marcus

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications. Objective.— To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil–induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome. Data Sources.— The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences. Conclusions.— The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.

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Immune Reconstitution Following Hematopoietic Cell Transplantation

Cited by 11 publications

References 196 publications

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation

Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation

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