scholarly journals Identification of an Essential IL15-STAT1-IRX3 Prosurvival Pathway in T Lymphocytes with Therapeutic Implications

2017 ◽  
Author(s):  
Stephan P. Persengiev
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
T Lymphocytes ◽  
Neural Development ◽  
Immune Cell ◽  
Apoptotic Pathway ◽  
Therapeutic Implications ◽  
Survival Pathway ◽  
Homeobox Transcription Factor ◽  
Cell Death Mechanisms

IRX3 homeobox transcription factor plays a role in neural development and in the pathogenesis of obesity and insulin resistance. T lymphocytes play an essential role in the pathogenesis of obesity and their expansion and differentiation is a tightly controlled process. Circulating cytokines trough activation of cell death mechanisms controls the number of CD4 and CD8 T cells, and failure to activate apoptosis is considered the main cause for their uncontrolled expansion. Here, the identification an essential anti-apoptotic pathway in T lymphocytes is presented, whereby IL-15 activation of Stat/Jak signaling cascade leads to induction of the IRX3 expression. IRX3, in turn, promotes T cells survival and self-renewal, at least partially, by controlling the expression of T-bet transcription factor eomesodermin (EOMES). The Stat/Jak signaling inhibition by Jak inhibitor 1 suppresses IRX3 transcription in T lymphocytes and tumor cell lines and increases apoptosis after growth factor deprivation. Our results demonstrate that IRX3 is essential in T lymphocytes differentiation and reveal that the IL-15-dependent IRX3 pro-survival pathway provides potential therapeutic target for regulation of T cell proliferation that has implications for immune cell malignancies, obesity and autoimmune diseases.

scholarly journals Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Meng-ge Yang ◽  
Li Sun ◽  
Jinming Han ◽  
Chao Zheng ◽  
Hudong Liang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factor ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Cell Types ◽  
Lymphoid Organ ◽  
Therapeutic Implications

AbstractTranscription factor RelB is a member of the nuclear factror-kappa B (NF-κB) family, which plays a crucial role in mediating immune responses. Plenty of studies have demonstrated that RelB actively contributes to lymphoid organ development, dendritic cells maturation and function and T cells differentiation, as well as B cell development and survival. RelB deficiency may cause a variety of immunological disorders in both mice and humans. Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system which involves a board of immune cell populations. Thereby, RelB may exert an impact on MS by modulating the functions of dendritic cells and the differentiation of T cells and B cells. Despite intensive research, the role of RelB in MS and its animal model, experimental autoimmune encephalomyelitis, is still unclear. Herein, we give an overview of the biological characters of RelB, summarize the updated knowledge regarding the role of RelB in different cell types that contribute to MS pathogenesis and discuss the potential RelB-targeted therapeutic implications for MS.

scholarly journals Identification of human immune cell subtypes most responsive to IL-1β–induced inflammatory signaling using mass cytometry

2021 ◽  
Vol 14 (673) ◽  
pp. eabc5763 ◽  
Author(s):  
Hema Kothari ◽  
Corey M. Williams ◽  
Chantel McSkimming ◽  
Fabrizio Drago ◽  
Melissa A. Marshall ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Peripheral Blood ◽  
Effector Memory ◽  
High Morbidity ◽  
Cytokine Storm ◽  
Mass Cytometry ◽  
Myeloid Dendritic Cells

IL-1β is a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19, and IL-1β blockade with anakinra and canakinumab during COVID-19 infection has entered clinical trials. Using mass cytometry of human peripheral blood mononuclear cells, we identified effector memory CD4+ T cells and CD4−CD8low/−CD161+ T cells, specifically those positive for the chemokine receptor CCR6, as the circulating immune subtypes with the greatest response to IL-1β. This response manifested as increased phosphorylation and, thus, activation of the proinflammatory transcription factor NF-κB and was also seen in other subsets, including CD11c+ myeloid dendritic cells, classical monocytes, two subsets of natural killer cells (CD16−CD56brightCD161− and CD16−CD56dimCD161+), and lineage− (Lin−) cells expressing CD161 and CD25. IL-1β also induced a rapid but less robust increase in the phosphorylation of the kinase p38 as compared to that of NF-κB in most of these immune cell subsets. Prolonged IL-1β stimulation increased the phosphorylation of the transcription factor STAT3 and to a lesser extent that of STAT1 and STAT5 across various immune cell types. IL-1β–induced production of IL-6 likely led to the activation of STAT1 and STAT3 at later time points. Interindividual heterogeneity and inhibition of STAT activation by anakinra raise the possibility that assays measuring NF-κB phosphorylation in response to IL-1β in CCR6+ T cell subtypes could identify those patients at higher risk of cytokine storm and most likely to benefit from IL-1β–neutralizing therapies.

scholarly journals Conclusive Identification of Senescent T Cells Reveals Their Abundance in Aging Humans

2020 ◽  
Author(s):  
Ricardo Iván Martínez-Zamudio ◽  
Hannah K. Dewald ◽  
Themistoklis Vasilopoulos ◽  
Lisa Gittens-Williams ◽  
Patricia Fitzgerald-Bocarsly ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Function ◽  
Immune Cell ◽  
Functional Decline ◽  
The Elderly ◽  
Cd8 T Cell ◽  
Cell Senescence ◽  
Healthy Humans

ABSTRACTAging leads to a progressive functional decline of the immune system, which renders the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this functional decline, however, remains unclear since methods to accurately identify and isolate senescent immune cells are missing. By measuring senescence-associated ß-galactosidase activity, a hallmark of senescent cells, we demonstrate here that healthy humans develop senescent T lymphocytes in peripheral blood with advancing age. Particularly senescent CD8+ T cells increased in abundance with age, ranging from 30% of the total CD8+ T cell population in donors in their 20s and reaching levels of 64% in donors in their 60s. Senescent CD8+ T cell populations displayed features of telomere dysfunction-induced senescence as well as p16-mediated senescence, developed in various T cell differentiation states and established gene expression signatures consistent with the senescence state observed in other cell types. On the basis of our results we propose that cellular senescence of T lymphocytes is a major contributing factor to the observed decline of immune cell function with advancing age and that immune cell senescence, therefore, plays a significant role in the increased susceptibility of the elderly to age-associated diseases and infection.

Chemokine receptors on peripheral blood T lymphocytes in children on peritoneal dialysis

2020 ◽  
pp. 089686082095129
Author(s):  
Maria Szczepańska ◽  
Łukasz Sędek ◽  
Joanna Bulsa ◽  
Bogdan Mazur ◽  
Danuta Zwolińska ◽  
...  
Keyword(s):  
T Cells ◽  
Peritoneal Dialysis ◽  
T Lymphocytes ◽  
Chemokine Receptors ◽  
Immune Cell ◽  
Flow Cytometric Analysis ◽  
T Cell Subsets ◽  
Healthy Children ◽  
Fluorescent Intensity ◽  
Surface Receptor

Background: Immune cell dysfunction is listed among complications resulting from chronic kidney disease (CKD). It could be associated with T-cells, which play a role in the lymphocytic migration and infiltration. However, the data on chemokine receptors expression on T-cells in patients with CKD particularly treated with peritoneal dialysis (PD) are still limited. Methods: The study aimed at multiparameter flow-cytometric analysis of the absolute numbers and percentage of T-cell subsets with surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptors’ combinations in 47 children treated with PD. Results: We found lower absolute numbers of total T lymphocytes, lymphocytes with surface CCR5, CXCR4+CCR5, CXCR3+CCR5 antigens and T-cells with CCR4, CCR4+CD4, CXCR3, CXCR3+CD4, and CD8 receptors. Lymphocytes T with CD4, CCR7, CD28+CCR7, CXCR3+CD8 antigens showed higher percentage in children on PD as compared to healthy children and opposite percentage values of CCR4+, CCR4+CD4+, CXCR3+ T lymphocytes were diminished. Mean fluorescent intensity for CCR7+, CCR7+CD45RO+, CCR7+CD28+, CXCR4+CD4+, CCR5+CD4+, CCR4+, CCR4+CD4+ T-cells was lower in the PD group than in healthy children. The analysis of correlation between T lymphocyte subpopulations with chemokine receptors and other parameters revealed positive correlation of CCR7+ and CCR7+CD28+ T-cells and weekly creatinine clearance, negative correlation between the percentage of CD45RO+CCR7 antigen positive T-cells and KT/Vurea. Summary: In conclusion, we could not confirm the phenomenon of earlier senescence of T-cells in children with CKD on PD treatment. This still requires further investigation. The higher percentage of T-cells with CCR7 surface receptor could be responsible for the increase of proliferation activity in this group of children.

scholarly journals Authentic Patient-Derived Hepatitis C Virus Infects and Productively Replicates in Primary CD4+and CD8+T LymphocytesIn Vitro

2017 ◽  
Vol 92 (3) ◽  
Author(s):  
Georgia Skardasi ◽  
Annie Y. Chen ◽  
Tomasz I. Michalak
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Hcv Rna ◽  
Biophysical Properties

ABSTRACTAccumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infectin vitrotwo closely related but functionally distinct immune cell types, CD4+and CD8+T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4+or CD8+T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4+than in CD8+T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4+and CD8+cells at estimated mean levels ± standard errors of the means of 6.7 × 102± 3.8 × 102and 1.2 × 102± 0.8 × 102copies/μg RNA, respectively (P< 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4+and in 1.2% of CD8+T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+and CD8+cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients.IMPORTANCEAlthough the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicatesin vitroin two closely related but functionally distinct types of T lymphocytes, CD4+and CD8+cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4+and CD8+T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C.

scholarly journals AB0138 INCREASED CD38 EXPRESSION LEVELS ON IMMUNE CELL SUBSETS IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1369.2-1370
Author(s):  
L. Ostendorf ◽  
P. Enghard ◽  
P. Durek ◽  
F. Heinrich ◽  
M. F. Mashreghi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Lymphocytes ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Immune Cell ◽  
Systemic Lupus ◽  
Cd38 Expression ◽  
Cd8 T Lymphocytes ◽  
Immune Cell Subsets

Background:Plasma Cells (PCs) are implicated in the pathogenesis of Systemic Lupus erythematosus (SLE) and their targeting proved a promising treatment modality. As there is a monoclonal therapeutic antibody targeting CD38 licensed for clinical use in multiple myeloma, plasma cell depletion via CD38 seems to represent a promising path in SLE treatment. While CD38 Is highly expressed on plasmacells, it is present on the surface of subsets of T and B lymphocytes as well as myeloid cells.Objectives:Here we aim to identify the differential expression of CD38 on peripheral blood leukocytes in SLE compared to healthy controls (HC) investigate the function of CD38+ T lymphocytesMethods:We performed flow cytometry to investigate the expression of CD38 on peripheral blood mononuclear cells of SLE patients (n=36) and HCs (n=20). We additionally analyzed the expression of T lymphocytes within the urine of patients with lupus nephritis as well as the skin of SLE patients. We investigated the inflammatory potential of CD38 positive memory T lymphocytes after stimulation and performed single-cell RNA sequencing analyses.Results:CD38 Expression is increased on certain immune cell subsets: Plasmablasts and unswitched Memory B cells, as well as plasmacytoid dendritic cells and CD16+ non-classical monocytes. We observed a drastic increase CD38 in both memory CD4 and CD8 T lymphocytes in SLE patients. These cells were mostly effector T cells (and not regulatory T cells) and expressed other markers of T cell activation and proliferation. We found an enrichment of CD38+ memory T cells in the urine of patients with lupus nephritis. After polyclonal stimulation of T cells, CD38+ produced less inflammatory cytokines. Preliminary single-cell sequencing results indicate that CD38+ CD8+ T-lymphocytes have decreased clonal diversity and that these cells express genes associated with exhaustion and type 1 interferon response.Conclusion:Increased CD38 expression on various lymphocyte subsets provides an additional rationale for investigating CD38-directed therapies in SLE. Targeting CD38 could not only deplete plasma cells but also has the potential to target interferon alpha producing plasmacytoid dendritic cells and modulate inflammatory T cell functions.Disclosure of Interests:Lennard Ostendorf: None declared, Philipp Enghard: None declared, Pawel Durek: None declared, Frederik Heinrich: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared

scholarly journals Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness

Folia Medica ◽  
2017 ◽  
Vol 59 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Snezhina M. Kandilarova ◽  
Atanaska I. Georgieva ◽  
Anastasiya P. Mihaylova ◽  
Marta P. Baleva ◽  
Valentina K. Atanasova ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Defense Mechanisms ◽  
Immune Cell ◽  
Treatment Success ◽  
Hbv Infection ◽  
Predictive Tool ◽  
Activated T Cells ◽  
Cd8 Cells ◽  
Treatment Naïve

AbstractBackground: The patient’s immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success.Aim: Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach.Patients and methods: A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues.Results: Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy.Conclusion: Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

scholarly journals Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b

2010 ◽  
Vol 207 (8) ◽  
pp. 1687-1699 ◽  
Author(s):  
Shuning Zhang ◽  
Mike Rozell ◽  
Raj K. Verma ◽  
Diana I. Albu ◽  
Danielle Califano ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Cytolytic Activity ◽  
Tcr Signaling ◽  
Expansion Phase ◽  
Cd8 T Lymphocytes ◽  
Cell Immunity

CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course of infection in the absence of Bcl11b, albeit in smaller numbers, and their Ag-specific cytolytic activity on a per-cell basis was altered, which was associated with reduced granzyme B and perforin.

scholarly journals Interplay of Monocytes and T Lymphocytes in COVID-19 Severity

2020 ◽  
Author(s):  
Lindsey E. Padgett ◽  
Huy Q. Dinh ◽  
Serena J. Chee ◽  
Claire E. Olingy ◽  
Runpei Wu ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Coagulation Factor ◽  
Effector Memory ◽  
Sugar Residue ◽  
Monocyte Subsets ◽  
Mass Cytometry ◽  
T Lymphocyte Subsets

ABSTRACTThe COVID-19 pandemic represents an ongoing global crisis that has already impacted over 13 million people. The responses of specific immune cell populations to the disease remain poorly defined, which hinders improvements in treatment and care management. Here, we utilized mass cytometry (CyTOF) to thoroughly phenotype peripheral myeloid cells and T lymphocytes from 30 convalescent patients with mild, moderate, and severe cases of COVID-19. We identified 10 clusters of monocytes and dendritic cells and 17 clusters of T cells. Examination of these clusters revealed that both CD14+CD16+ intermediate and CD14dimCD16+ nonclassical monocytes, as well as CD4+ stem cell memory T (TSCM) cells, correlated with COVID-19 severity, coagulation factor levels, and/or inflammatory indicators. We also identified two nonclassical monocyte subsets distinguished by expression of the sugar residue 6-Sulfo LacNac (Slan). One of these subsets (Slanlo, nMo1) was depleted in moderately and severely ill patients, while the other (Slanhi, nMo2) increased with disease severity and was linked to CD4+ T effector memory (TEM) cell frequencies, coagulation factors, and inflammatory indicators. Intermediate monocytes tightly correlated with loss of naive T cells as well as an increased abundance of effector memory T cells expressing the exhaustion marker PD-1. Our data suggest that both intermediate and non-classical monocyte subsets shape the adaptive immune response to SARS-CoV-2. In summary, our study provides both broad and in-depth characterization of immune cell phenotypes in response to COVID-19 and suggests functional interactions between distinct cell types during the disease.One Sentence SummaryUse of mass cytometry on peripheral blood mononuclear cells from convalescent COVID-19 patients allows correlation of distinct monocyte and T lymphocyte subsets with clinical factors.

Abstract 005: Axl Controls Survival of the CD4+ T Lymphocytes in Salt-dependent Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Vyacheslav A Korshunov ◽  
Angie Hughson ◽  
Craig N Morrell ◽  
Deborah J Fowell ◽  
Sri N Batchu
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Wild Type ◽  
Salt Hypertension ◽  
The Media ◽  
Bone Marrow Derived Cells ◽  
Blood Leukocyte ◽  
Carboxyfluorescein Succinimidyl Ester

Introduction: Axl, a receptor tyrosine kinase, is required for vascular and immune cell survival. We sought to investigate the effects of Axl on T lymphocyte survival during deoxycorticosterone acetate (DOCA)-salt hypertension in mice. Methods and Results: We found significant reduction in systolic blood pressure (BP) after 5-6 weeks of DOCA-salt in RAG1-/- mice after adoptive transfer of CD4+ T cells from Axl knockout (Axl-/- →RAG1-/-) compared to transferred CD4+ T cells from wild type (Axl+/+ →RAG1-/-) mice. Media area of the mesenteric artery was significantly lower in Axl-/- →RAG1-/- (4.2±0.7x10 3 m 2 ) vs. Axl+/+ →RAG1-/- (6.0±0.9x10 3 m 2 ) or Axl+/+ (6.8±0.6x10 3 m 2 ) mice. There was significant decrease in interferon gamma production by the T cells from Axl-/- (396±23 ng/mL) compared to Axl+/+ (512±42 ng/mL) after T h 1-priming. The number of carboxyfluorescein succinimidyl ester-positive cells in 6 th division was dramatically declined in Axl-/- (~0.3%) vs. Axl+/+ (~1.8%) in culture. Accordingly, we found lower number of lymphocytes in blood from Axl-/- (4.5±0.7x10 9 ) compared to Axl+/+ (7.8±0.7x10 9 ) mice. Blood leukocyte apoptosis was 2.5-fold higher in Axl-/- mice. We next investigated repopulation capacities of the hematopoietic cells from Axl-/- vs. Axl+/+ mice. There was significant decrease in Axl-/- CD3+ T cells (21±3 %) than Axl+/+ (49±3 %) in spleen after 8 weeks of competitive repopulation of bone marrow-derived cells. However, we found even greater reduction of Axl-/- T lymphocytes (15±1 %) vs. Axl+/+ T lymphocytes (52±6 %) in peripheral blood after 8 weeks of competitive repopulation. Finally, percentage of apoptotic cells was the greatest in the media (20±7 %) and adventitia (13±5 %) from Axl-/- →RAG1-/- mice compared to vascular apoptosis (6-14 % in media; and 6-9 % in adventitia) in other groups after 6 weeks of DOCA-salt. Conclusions: Our data suggest that Axl-dependent survival of the T lymphocytes is crucial for the late increase in BP in DOCA-salt hypertension.

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