Dynamic Expression of Qa-2 during Acute Graft Rejection

Lü, Nan; Wang, Chuanxin; Xj, Yang; Zhao, Sixiang; Li, Xiangdong; Li, Xiaoli; Jiang, Hong; Feng, Jinzhou; Zhang, Yi; Zou, Xiong

doi:10.2119/molmed.2010.00133

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…However, NT-ESC samples showed a slight increase of Qa- 2 caused by the SCNT procedure effect not TSA (Figure 1 (s), Supplementary data). Qa- 2 is another member of the MHC Ib family, which can suppress NK cells through interacting Lys49c receptor on NK cells [ 25 , 26 ] and interfere in immune tolerance. Literature showed that Qa-2 has inhibitory effect even at low expression level and is able to protect the cells against graft rejection [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level

Farahi

Hosseini

Ghanbarian

et al. 2022

Stem Cells International

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Pluripotent stem cells (PSCs) are considered as a potent tool for use in regenerative medicine. Highly efficient generation of PSCs through chromatin modulators such as trichostatin A (TSA) might change their MHC molecule expression profile. The efficiency of PSC generation and their immunogenicity is major obstacles for clinical use. Hence, we aim to investigate whether the use of TSA during PSC generation affects MHC expression level. Three PSC lines were generated by iPSCs, NT-ESCs, and IVF-ESCs’ reprogramming methods from B6D2F1 mouse embryonic fibroblast cells. Established PSC lines were characterized by alkaline phosphatase assay (ALP) and immunocytochemistry. Their chromosome fidelity was checked by karyotyping. The expression level of pluripotent genes (oct4, nanog, sox2, klf4), HDACs (hdac1, hdac2, and hdac3), and immune-related genes (including Qa-1, Qa-2, H2kb, H2kd, H2db, H2db, CIITA, H2-IE-βb, H2-IE-βd) in iPSC and ESC lines were assessed by real-time PCR analysis. The presence of MHC molecules on the surface of pluripotent stem cells was also checked by flow cytometry technique. Significant increase of pluripotency markers, oct4, nanog, sox2, and klf4, was observed in 100 nM TSA-treated samples. 100 nM TSA induced significant upregulation of H2db in generated iPSCs. H2-IE-βd was remarkably downregulated in 50 and 100 nM TSA-treated iPSC lines. The expression level of other immune-related genes was not greatly affected by TSA in iPSC and NT-ESC lines. It is concluded that the use of short-term and low concentration of TSA during reprogramming in PSC generation procedure significantly increases PSC generation efficiency, but do not affect the MHC expression in established cell lines, which is in the benefit of cell transplantation in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level

Farahi

Hosseini

Ghanbarian

et al. 2022

Stem Cells International

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“…Our previous study with mice skin transplantation model showed time-dependent dynamic expression of Qa-2 (the murine homolog of HLA-G) mRNA on PBMCs during entire episodes of AR, which is closely related to AR occurrence and immunosuppressive treatment [15,16]. Recently, Racca et al reported that HLA-G1 mRNA levels in PBMCs from patients with AR are below the median value of stable recipients [17].…”

Section: Discussionmentioning

confidence: 99%

HLA-G on peripheral blood CD4+ T lymphocytes: a potential predictor for acute renal rejection

Lü¹,

Zhang²,

Zou³

et al. 2011

Transplant International

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Summary HLA‐G Expression in grafts and serum has been shown to improve graft acceptance. However, its expression on peripheral blood lymphocytes (PBLs) during acute rejection (AR) remains unknown. In this study, we serially monitored HLA‐G expression on CD4+ and CD8+ PBLs of 66 recipients undergoing renal transplantation using flow cytometry at different time points before and after transplantation, as well as during AR episode. In stable recipients, HLA‐G expression on CD4+ PBLs declined during the first week after transplantation and increased continuously with immunosuppressive therapy. Then, expression declined gradually after 1 month and remained at a higher level compared with pretransplantation. When AR occurred, HLA‐G expression decreased significantly compared with the stable level. In three recipients suffering from recurrent rejection, it remained at a low level despite impact immunosuppressive treatment. With mix lymphocyte assay, HLA‐G+ CD4+ T cells showed inhibitory role on proliferation of peripheral blood mononuclear cell. HLA‐G expression on CD8+ PBLs was almost undetectable at different time points in the recipients and healthy controls. Our results suggest that HLA‐G on CD4+ PBLs might provide a potential marker for the early diagnosis of renal AR and for the immunosuppressive status of recipients.

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“…In contrast, treatment with immunosuppressive drugs upregulated Qa-2 expression in both grafts and PBLs and prolonged the survival of skin allografts. Qa-2 expression subsequently decreased during allograft rejection (52). These results clearly point to an inverse relationship between Qa-2 levels and allograft rejection.…”

Section: The Murine Non-classical Mhc Complex Qa-2 Its Role In Embrymentioning

confidence: 99%

New Insights Into the Role of Qa-2 and HLA-G Non-classical MHC-I Complexes in Malignancy

2018

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It is well established that the immune system can identify and destroy neoplastic transformed cells in a process known as immunosurveillance. Most studies have focused on the classical major histocompatibility complex (MHC) class Ia molecules, which are known to play an important role on the presentation of tumor antigens to the immune system in order to activate a response against tumor cells. However, a larger family of non-classical MHC class Ib-related molecules has received less attention. In this mini-review, we discuss the role of class Ib murine Qa-2 and its proposed human HLA-G homolog on immunosurveillance during embryogenesis and cancer. Whereas, both HLA-G and Qa-2 are involved in immune tolerance in pregnancy, the current evidence suggests that they play opposite roles in cancer. HLA-G appears to promote tumor progression while Qa-2 acts as a tumor suppressor awaking the immune system to reject tumor cells, as suggested by studies on different cancer cell models, such as melanoma, lymphoma, lung carcinoma, and our own results in mammary carcinoma.

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Dynamic Expression of Qa-2 during Acute Graft Rejection

Cited by 3 publications

References 35 publications

The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level

The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level

HLA-G on peripheral blood CD4+ T lymphocytes: a potential predictor for acute renal rejection

New Insights Into the Role of Qa-2 and HLA-G Non-classical MHC-I Complexes in Malignancy

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