Tonsillar CD4+CD25+ Regulatory T Cells from IgA Nephropathy Patients Have Decreased Immunosuppressive Activity in Experimental IgA Nephropathy Rats

Introduction: Adaptive regulatory T cells (Tr1) are induced in the periphery by environmental stimuli. CD73 expression and adenosine (ADO) production by tumor cells may influence Tr1 generation and their immunosuppressive activity. Material and Methods: Tr1 were generated in co-cultures of CD4+CD25neg T cells, autologous immature dendritic cells (iDC), and irradiated ADO-producing CD73+ or non-producing CD73neg breast cancer (BrCa) cell lines (TU). The expression of ectonucleotidases and other surface markers on Tr1 was determined by flow cytometry. Tr1-mediated suppression of proliferation was evaluated in CFSE-based assays. Luciferase-based ATP detection assays and mass spectrometry were used to measure ATP hydrolysis and ADO levels. Cytokine levels were measured by ELISA or Luminex. CD73 expression on tumor cells or T cells in TU tissues was assessed by immunofluorescence. Results: CD73+ TU induced higher numbers of Tr1 cells (p < 0.01) than CD73neg TU. Tr1TU73+ hydrolyzed more exogenous ATP, produced more ADO, and mediated higher suppression than Tr1TU73neg (p < 0.05 for all). ARL67156, an ectonucleotidase inhibitor, and ZM241385, A2A receptor antagonist, reduced suppression of proliferation mediated by Tr1TU73+ cells (p < 0.01). Basal-like primary BrCa cells expressed higher levels of ectonucleotidases and induced more Tr1 than less aggressive primary luminal-like BrCa. Conclusion: BrCa producing ADO (CD73+ TU) favor the induction of Tr1, which expresses CD39 and CD73, hydrolyzes ATP to ADO, and effectively suppresses anti-tumor immunity.

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Buserelin Inhibits the Immunosuppressive Activity of Regulatory T Cells through the Protein Kinase A Signaling in a Central Precocious Puberty Model

Immunological Investigations ◽

10.1080/08820139.2021.1885437 ◽

2021 ◽

pp. 1-15

Author(s):

Hua Li ◽

Xiao-Xia Zhu ◽

Jin-Bo Xiang ◽

Lei Jian

Keyword(s):

T Cells ◽

Protein Kinase ◽

Regulatory T Cells ◽

Protein Kinase A ◽

Precocious Puberty ◽

Central Precocious Puberty ◽

Immunosuppressive Activity ◽

Kinase A

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Activation of Gonadotropin-releasing Hormone Receptor Impedes the Immunosuppressive Activity of Decidual Regulatory T Cells via Deactivating the Mechanistic Target of Rapamycin Signaling

Immunological Investigations ◽

10.1080/08820139.2021.1937208 ◽

2021 ◽

pp. 1-17

Author(s):

Xuejin Wang ◽

Liangying Zhong ◽

Qiaodan Liu ◽

Peiya Cai ◽

Peiru Zhang ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Hormone Receptor ◽

Gonadotropin Releasing Hormone ◽

Target Of Rapamycin ◽

Immunosuppressive Activity ◽

Releasing Hormone ◽

Mechanistic Target Of Rapamycin ◽

Gonadotropin Releasing Hormone Receptor

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Pathologic tonsillar findings similar to IgA nephropathy and the role of tonsillectomy in a patient with nephrotic syndrome

BMC Nephrology ◽

10.1186/s12882-019-1580-y ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Takuji Enya ◽

Tomoki Miyazawa ◽

Kohei Miyazaki ◽

Rina Oshima ◽

Yuichi Morimoto ◽

...

Keyword(s):

T Cells ◽

Nephrotic Syndrome ◽

Regulatory T Cells ◽

Iga Nephropathy ◽

Immunosuppressive Agents ◽

Chronic Tonsillitis ◽

Pathological Findings ◽

Lymphoid Follicles ◽

Crypt Epithelium ◽

Self Tolerance

Abstract Background: The pathological findings of tonsils in IgA nephropathy include the expansion of T-cell nodules around lymphoid follicles and abnormal reticulation of the crypt epithelium in contrast to chronic tonsillitis. Recently, several studies have reported that regulatory T cells play an important role in the maintenance of self-tolerance, an abnormality that is involved in the onset of nephrotic syndrome (NS). We encountered a patient of 28-year-old male with frequently relapsing nephrotic syndrome (FRNS) and chronic tonsillitis whose tonsils demonstrated pathological findings similar to those of IgA nephropathy. Case presentation A patient had developed NS at the age of 5 years, and was pathologically diagnosed with minimal change disease (MCD), for which he received various immunosuppressive agents as treatment for recurrence. Because tonsillitis often triggers the recurrence of NS, a tonsillectomy was performed for chronic tonsillitis at the age of 25 years. Immunohistochemical staining of his tonsils showed the expansion of CD4 positive lymphocytes around the lymphoid follicles and abnormal reticulation of the crypt epithelium. The number of peripheral blood CD4+CD25+ regulatory T cells increased, and the frequency of relapses decreased after tonsillectomy. Conclusion A similar self-tolerance abnormality exists in NS and IgA nephropathy; therefore, tonsillectomy might become a novel therapeutic approach for FRNS to redress the unbalanced self-tolerance and to remove the tonsillar focal infection. Further studies are necessary to verify the clinical efficiency of tonsillectomy for FRNS with recurrent episodes triggered by tonsillitis.

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