Human Leukocyte Antigen (HLA) Class II Expression on Regulatory T Cells (Tregs) Isolated from Discarded Human Thymus is Induced by In Vitro Expansion Conditions

Dijke, E.; Ellis, T.; Larsen, I.; Rebeyka, Ivan M.; Freed, Darren H.; Al-Aklabi, Mohammed; Levings, Megan K.; West, Lori J.

doi:10.1016/j.healun.2020.01.755

Cited by 1 publication

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“…T reg cells were obtained from our collaborators (MKL) after expansion, as previously described (protocol F). 17 In order to determine if the suppressive capacity of NK reg cells on CD4 + T cells is contact dependent the above procedures were followed using a 96-well transwell plate (Corning, Corning, NY, USA). Additionally, supernatant from a 96-h 1:1 NK reg versus CD4 + T-cell suppression assay was cultured with fresh allogeneic activated CD4 + T cells for 72 h and then analyzed.…”

Section: Methodsmentioning

confidence: 99%

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CD56brightCD16– natural killer cells as an important regulatory mechanism in chronic graft-versus-host disease

et al. 2022

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Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity after Hematopoietic Stem Cell Transplantation (HSCT). In large patient populations, we have shown a CD56bright Natural Killer population to strongly associate with a lack of cGvHD and we hypothesize that these cells function to suppress cGvHD. We aimed to isolate and define the characteristics of NKreg cells associated with suppression of cGvHD. Immunophenotypic evaluation of a large pediatric population found the CD56bright NK population associated with a lack of cGvHD to be perforin-, Granzyme B-, and CD335+. Transcriptome analysis of a small patient cohort of CD56bright compared to CD56dim NK cells found the NKreg cells to also overexpress Granzyme K, IL-7R, GPR183, RANK, GM-CSFR, TCF7, and IL23A. Further analysis of this CD56bright NKreg population found a subpopulation that overexpressed IRF1, and TNF. We also found that viable NKreg cells may be isolated by sorting on CD56+ and CD16- NK cells, and this population can suppress allogeneic CD4+ T cells, but not Treg cells or CD8+ T cells through a non-cytolytic, cell-cell contact dependent mechanism. Suppression was not reliant upon the NKp44, NKp46, or GPR183 receptors. Additionally, NKreg cells do not kill leukemic cells. Moreover, this is the first paper to clearly establish that a CD56brightCD3-CD16-perforin- NKreg population associates with a lack of cGvHD and has several unique characteristics, including the suppression of helper T cell function in vitro. With further investigation we may decipher the mechanism of NKreg suppression and operationalize expansion of NKreg cells associated with cGvHD suppression.

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Section: Methodsmentioning

confidence: 99%

“…T reg cells were obtained from our collaborators [M.K.L] after expansion, as previously described (protocol F). 17 To determine if the suppressive capacity of NK reg cells on CD4 + T cells is contact dependent the above procedures were followed using a 96-well transwell plate (Corning, Corning, NY, USA).…”

Section: Evaluation Of Nk Reg Cell Suppressionmentioning

confidence: 99%