The Role of T Cells in Hematopoietic Stem Cell Engraftment

Hexner, Elizabeth O.

doi:10.1100/tsw.2006.47

Cited by 4 publications

(3 citation statements)

References 54 publications

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“… 16 , 17 , 18 , 19 In the absence of sufficient myelo- and lymphoablation these non-HSC facilitating cells play a more prominent role in promoting HSC engraftment. T cells are known to facilitate engraftment by virtue of marrow-directed graft-vs-host activity 16 , 19 , 20 , 21 , but other populations and mechanisms have been implicated in enhancing donor HSC engraftment as well. 18 , 22 , 23 , 24 We examined by immunophenotype profiling the different lymphocyte subsets present in fresh versus cryopreserved products.…”

Section: Discussionmentioning

confidence: 99%

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

Bankova¹,

Caveney²,

Yao³

et al. 2022

Transplantation and Cellular Therapy

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Background As a result of the COVID-19 widespread pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. Objectives To compare the outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). Study design We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 as compared to 60 consecutive patients who received fresh allografts prior to the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment, graft failure (GF) and secondary outcomes were overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved versus prospectively collected fresh apheresis samples. Results Compared to fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced intensity conditioning (RIC) allo-HCT with median times to engraftment of 24 days vs 18 days ( P = .01) and 27 days vs 18 days ( P = .069), respectively. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) vs only one of 60 patients (1.7 %) in the fresh cohort ( P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid and T-cell donor chimerism at 1 month. OS and RFS were inferior for cryograft recipients with hazard ratio [HR (95%Cl)]: 2.16 (1.00, 4.67) and 1.90 (0.95, 3.79), respectively. Using an extended immunophenotype analysis we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both decrease in total cell viability and significantly reduced absolute numbers of NK cells (CD3 − CD56 + ) in the cryopreserved apheresis samples. Conclusion In this single institution study we note delayed engraftment and a trend toward clinical inferiority of cryopreserved vs fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

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Section: Discussionmentioning

confidence: 99%

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

Bankova¹,

Caveney²,

Yao³

et al. 2022

Transplantation and Cellular Therapy

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“…GVHD pathophysiology is complex and not well understood, but is critically dependent on the differentiation of donor-derived T cells into subsets (19). Furthermore, which T cell subsets are necessary for the development of pulmonary GVHD has not been fully characterized, although Th1 cells have been implicated in many features of GVHD (12).…”

Section: Discussionmentioning

confidence: 99%

Protective Role of T-bet and Th1 Cytokines in Pulmonary Graft-versus-Host Disease and Peribronchiolar Fibrosis

Gowdy

Nugent

Martinu

et al. 2012

Am J Respir Cell Mol Biol

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T-box expressed in T cells (T-bet) is a critical transcription factor for T helper (Th) 1 responses. Although Th1 cells are thought to contribute to certain alloimmune responses, their role in pulmonary graft-versus-host disease (GVHD) is uncertain. We have established a murine model of acute pulmonary GVHD after hematopoietic cell transplant (HCT) and inhaled LPS exposure. We tested the hypothesis that pulmonary GVHD can occur independent of Th1 cells using T-bet-deficient donors. B10.BR(H2(k)) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with cells from either C57Bl/6J(H2(b)) mice (Allo wild-type [WT] or SynWT) or C57Bl/6J mice lacking T-bet (AlloTbet(-/-) or SynTbet(-/-)). After HCT, mice were exposed daily to aerosolized LPS and subsequently bronchoalveolar lavage and lung tissue were analyzed for cytokines, lymphocytic inflammation, pathology, and fibrosis. Independent of LPS exposure, AlloTbet(-/-) mice developed pulmonary GVHD manifested by lymphocytic inflammation. Furthermore, AlloTbet(-/-) mice developed features of chronic pulmonary GVHD, including increased peribronchiolar fibrosis and collagen content. LPS exposure increased neutrophil recruitment and decreased static compliance in AlloTbet(-/-) mice as compared with LPS-exposed AlloWT mice or LPS-exposed SynTbet(-/-) mice. In addition, LPS-exposed AlloTbet(-/-) mice had increased pulmonary IL-17, IL-13, and Th17 cells, and diminished regulatory T cells compared with the other groups. Our results demonstrate that Th1 cytokines are dispensable in pulmonary GVHD. In the absence of T-bet, there is increased production of Th17 and Th2 cytokines that is associated with peribronchiolar fibrosis and is further enhanced by LPS. These results suggest that the interplay between local innate immunity and non-Th1 T cell subsets contribute to chronic pulmonary GVHD.

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“…These cells are exposed to antigens that were not present in the transplant donor, and are thus recognized as foreign. The effector cells in the GVHD reaction are donor T cells, which differentiate self from foreign using the major histocompatibility complex (MHC) of the donor (Hexner, 2006). HLAs expressed on the cell surfaces of the recipient cells are the gene products of the recipient MHC.…”

Section: Background On Gvhdmentioning

confidence: 99%

Mucosal graft‐vs‐host disease

Lew

Smith

2007

Oral Diseases

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Graft‐vs‐host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Indications for HSCT have greatly expanded, and more patients are undergoing HSCT today than ever before. In addition, the options for immunosuppressive therapy for both prevention and treatment of GVHD have also expanded. These changes have in turn altered the landscape of this disease. We have reviewed the current literature on this subject and presented an update on this disease with a particular emphasis on mucosal manifestations.

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The Role of T Cells in Hematopoietic Stem Cell Engraftment

Cited by 4 publications

References 54 publications

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

Protective Role of T-bet and Th1 Cytokines in Pulmonary Graft-versus-Host Disease and Peribronchiolar Fibrosis

Mucosal graft‐vs‐host disease

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