Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy

ObjectiveDiabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN.Research design and methodsThe expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR−/−), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a.ResultsCompared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR−/− diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR−/− diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage.ConclusionsC3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.

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Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single center

Blood ◽

10.1182/blood.2018885244 ◽

2019 ◽

Vol 133 (24) ◽

pp. 2586-2596 ◽

Cited By ~ 4

Author(s):

Giuliana Giardino ◽

Nesrine Radwan ◽

Patra Koletsi ◽

Deborah M. Morrogh ◽

Stuart Adams ◽

...

Keyword(s):

Risk Factor ◽

T Cell ◽

T Lymphocytes ◽

Digeorge Syndrome ◽

Cell Number ◽

Physiological Age ◽

Upper Respiratory Tract ◽

Street Hospital ◽

Age Related ◽

Tract Infections

Abstract DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.

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4.20 T+ cell number increase in the spleen of chicken embryos in GVH-R serial transfer experiments

Developmental & Comparative Immunology ◽

10.1016/0145-305x(89)90110-9 ◽

1989 ◽

Vol 13 (4) ◽

pp. 392

Author(s):

B. Fedecka-Bruner ◽

J. Desveaux-Chabrol ◽

F. Dieterlen-Liévre

Keyword(s):

T Cell ◽

Cell Number ◽

Serial Transfer ◽

Chicken Embryos ◽

Number Increase

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High stromal Foxp3-positive T cell number combined to tumor stage improved prognosis in head and neck squamous cell carcinoma

Oral Oncology ◽

10.1016/j.oraloncology.2017.02.023 ◽

2017 ◽

Vol 67 ◽

pp. 183-191 ◽

Cited By ~ 9

Author(s):

Nadège Kindt ◽

Géraldine Descamps ◽

Imelda Seminerio ◽

Justine Bellier ◽

Jérôme R. Lechien ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Stage ◽

Cell Number ◽

Neck Squamous Cell Carcinoma

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T-Cell Number, Nutritional Status, and HIV

Health of HIV Infected People ◽

10.1016/b978-0-12-800767-9.00021-2 ◽

2015 ◽

pp. 367-387

Author(s):

Elisa Maritza Linares Guerra ◽

Sergio Santana Porbén

Keyword(s):

T Cell ◽

Nutritional Status ◽

Cell Number

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Effects of the ablation of the left cerebral cortex on T-cell number and cell-medaited responses in the mouse

International Journal of Immunopharmacology ◽

10.1016/0192-0561(80)90046-6 ◽

1980 ◽

Vol 2 (3) ◽

pp. 156 ◽

Cited By ~ 4

Author(s):

G. Renoux ◽

K. Bizière ◽

M. Renoux ◽

L. Gyenes ◽

D. Degenne ◽

...

Keyword(s):

Cerebral Cortex ◽

T Cell ◽

Cell Number

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Relationship of CD8+ T cell noncytotoxic anti-HIV response to CD4+ T cell number in untreated asymptomatic HIV-infected individuals

Blood ◽

10.1182/blood-2001-11-0078 ◽

2002 ◽

Vol 99 (11) ◽

pp. 4225-4227 ◽

Cited By ~ 28

Author(s):

JoAnn C. Castelli ◽

Steven G. Deeks ◽

Stephen Shiboski ◽

Jay A. Levy

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Cell Number ◽

Current Recommendation ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Cd8 Cell ◽

Asymptomatic Individuals ◽

Relationship Of ◽

Cd4 Cell

During chronic HIV infection, asymptomatic individuals demonstrate a strong CD8+ cell noncytotoxic antiviral response (CNAR). With the onset of symptoms or reduction in CD4+ cell counts, CNAR decreases. Presently, it is recommended that infected individuals receive antiretroviral therapy if CD4+ cell counts fall below 350 cells/μL. To determine whether CNAR lends support to this recommendation for initiation of antiretroviral treatment, we examined CNAR in 20 healthy, untreated, HIV-infected men exhibiting a range of CD4+ cell numbers. Our results indicate that the asymptomatic untreated HIV-infected individuals with less than 300 CD4+ cells/μL had a significantly lower CNAR than those with higher CD4+ cell counts. These data on CNAR in untreated, healthy, HIV-infected individuals support the current recommendation for when to initiate antiretroviral therapy.

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Significant Expansion of Myeloid Derived Suppressor Cells in Patients with High- Risk Breast Cancer Treated with Dose Dense Adjuvant Chemotherapy

Blood ◽

10.1182/blood.v112.11.4653.4653 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4653-4653

Author(s):

James E Talmadge ◽

Elizabeth Reed ◽

Kenneth Cowan ◽

Dmitry Gabrilovich ◽

Phyllis Warkentin ◽

...

Keyword(s):

T Cell ◽

Cancer Patients ◽

Mononuclear Cells ◽

Flow Analysis ◽

Suppressor Cells ◽

Cell Number ◽

Myeloid Derived Suppressor Cells ◽

Breast Cancers ◽

Dose Dense ◽

And Function

Abstract Myeloid derived suppressor cells (MDSCs) have been reported to be expanded in cancer patients, following growth factor administration and after chemotherapy. These cells have been associated with a loss of T-cell number and function and provide one mechanism of immune evasion. We examined the effect of dose dense chemotherapy on immune phenotypes and function in patients with breast cancers 4 cms or larger and/or four or more involved nodes. The adjuvant therapy was dose-dense doxorubicin, cyclophosphamide (AC) followed by paclitaxel (P), then 33 doses of radiation (R). Blood samples were obtained and studied prior to therapy, 1 week post AC and 1, 15 and 21 weeks post P and then 3, 6 and 12 months later. Flow cytometric analyses of cellular phenotypes were done on these blood specimens and compared to the levels prior to therapeutic intervention and to normal age and sex matched donors. Twenty-three pts have been followed a median of 29 months (range 5.5–50.5 months) from study entry. Two patients relapsed 8 and 23 months after diagnosis. T-cell CD-4 numbers declined following AC from an average of 4.9±0.5 ×106/ml to 1.7±0.3×106/ml, but increased to an average of 2.7± 0.3 × 106/ml, 21 weeks after P or 12 weeks after R. In this study the MDSCs were defined as Lin- (CD3, CD19, CD14 and CD13), HLA-DR- and CD33+. The numbers of MDSCs, which in normal donors were 0.62±0.16×106/ml and in the cancer patients at diagnosis were 11.8±9.6×106/ml increased to 58.4±25.9×106/ml 15 weeks after R. They remained significantly elevated through one year after diagnosis when they were 27.3±12.3×106/ml. The majority of the MDSCs had a high side scatter and forward scatter by flow analysis suggesting a granulocytic commitment rather than a monocytic commitment. The increase in MDSC numbers was apparently associated with R as the numbers of MDSCs were not significantly increased by AC (15.7±13.5×106/ml) or P (10.9±6×106/ml) one week following completion of each cycle of dose dense therapy. In association with the increase in MDSCs there was a significant decrease in PHA proliferation by the peripherial blood mononuclear cells (MNCs) and suppressive activity by irradiated MNC for allergenic lymphocytes.

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