scholarly journals After Experimental Trypanosoma cruzi Infection, Dying Hepatic CD3+TCRαβ+B220+ T Lymphocytes Are Rescued from Death by Peripheral T Cells and Become Activated

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 717
Author(s):  
Natalia Vacani-Martins ◽  
Marcelo Meuser-Batista ◽  
Otacilio C. Moreira ◽  
Cynthia Machado Cascabulho ◽  
Daniela Gois Beghini ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Trypanosoma Cruzi ◽  
T Lymphocyte ◽  
Complex Interactions ◽  
Peripheral T Cells ◽  
Activated T Lymphocytes ◽  
Fas L ◽  
Unusual Phenotype ◽  
Cruzi Infection

The unusual phenotype of CD3+ T lymphocyte expressing B220, a marker originally attributed to B lymphocytes, was first observed in the liver of Fas/Fas-L-deficient mice as a marker of apoptotic T lymphocytes. However, other CD3+B220+ T lymphocyte populations were later described in the periphery as functional cytotoxic or regulatory cells, for example. Then, in this work, we studied whether hepatic CD3+B220+ T lymphocytes could play a role in experimental Trypanosoma cruzi infection. In control and infected mice, we observed two subpopulations that could be discerned based on CD117 expression, which were conventional apoptotic CD3+B220+(CD117−) and thymus-independent CD3+B220+CD117+ T lymphocytes. Regardless of CD117 expression, most B220+ T lymphocytes were 7AAD+, confirming this molecule as a marker of dying T cells. However, after infection, we found that around 15% of the CD3+B220+CD117+ hepatic population became B220 and 7AAD negative, turned into CD90.2+, and upregulated the expression of CD44, CD49d, and CD11a, a phenotype consistent with activated T lymphocytes. Moreover, we observed that the hepatic CD3+B220+CD117+ population was rescued from death by previously activated peripheral T lymphocytes. Our results extend the comprehension of the hepatic CD3+B220+ T lymphocyte subpopulations and illustrate the complex interactions that occur in the liver.

scholarly journals Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells

1987 ◽  
Vol 132 (1) ◽  
pp. 43-57
Author(s):  
H. Wekerle ◽  
D. Sun ◽  
R. L. Oropeza-Wekerle ◽  
R. Meyermann
Keyword(s):  
T Cells ◽  
Nervous System ◽  
T Lymphocytes ◽  
Interferon Gamma ◽  
Glial Cells ◽  
T Lymphocyte ◽  
Cell Contact ◽  
Immune Reactivity ◽  
Antigen Specificity ◽  
Activated T Lymphocytes

The vertebrate central nervous system (CNS) has been traditionally thought to be inaccessible for the passenger lymphocytes of the immune system. This does not seem to be the case: activated T-lymphocytes can readily cross the endothelial blood-brain barrier (BBB) and some glial cells, notably the astrocytes, seem to be programmed to act as most efficient and complex partners for antigen-specific T-lymphocytes. We used myelin basic protein (MBP) specific permanent rat T-lymphocyte lines as probes to assess the immune status of the CNS. These cells, upon activation in vitro, are able to transfer lethal, experimentally induced autoimmune-encephalomyelitis (EAE) to normal syngeneic recipients. Activated T-lymphocytes, but not resting ones, can break through the BBB irrespective of their antigen specificity. Immune surveillance of the CNS thus seems to be executed by activated T-lymphocytes. Having crossed the BBB, the activated T-cells interact with local glial cells by releasing factors, including interferon-gamma, which induced astrocytes to synthesize and express, on their membranes, class II major histocompatibility antigens (Ia determinants), which are critically required for immunogenic presentation of antigens to T-cells. Indeed, Ia-induced astrocytes of the CNS (and the Schwann cells of peripheral nerves) are efficient antigen presenter cells, which are able strongly to up-regulate antigen-reactive T-lymphocytes. In addition, it has recently been shown that at least some astrocytes are able to down-regulate immune cells. Some, but not all, astrocytes are capable of suppressing activation of T-cells. This suppression can be modulated by interferon-gamma, and is sensitive to irradiation. The question of whether suppression is mediated by direct cell-to-cell contact or via soluble mediators (e.g. apolipoprotein E) is under investigation. Astrocytes have been found to be most subtle regulators of immuno-competent T-cells. Most probably they are centrally involved in physiological immune reactivity of the CNS, and it will be tempting to learn how far glial cells are involved in transmitting regulatory signals between the immune and nervous systems.

scholarly journals Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Treg Cell ◽  
T Lymphocyte ◽  
Extrapulmonary Tuberculosis ◽  
Lymphocyte Activation ◽  
Content Type ◽  
T Lymphocyte Activation ◽  
Previously Treated

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.

scholarly journals Benznidazole Treatment following Acute Trypanosoma cruzi Infection Triggers CD8+ T-Cell Expansion and Promotes Resistance to Reinfection

2002 ◽  
Vol 46 (12) ◽  
pp. 3790-3796 ◽  
Author(s):  
Bianca Perdigão Olivieri ◽  
Vinícius Cotta-de-Almeida ◽  
Tania Araújo-Jorge
Keyword(s):  
T Lymphocytes ◽  
Trypanosoma Cruzi ◽  
Immune Regulation ◽  
Immune Dysregulation ◽  
Direct Role ◽  
Parasite Replication ◽  
The Impact ◽  
Shed Light ◽  
Cruzi Infection

ABSTRACT Many studies have shed light on the mechanisms underlying both immunoprotection and immune dysregulation arising after Trypanosoma cruzi infection. However, little is known about the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide), the drug available for clinical treatment of the infection, on the immune system in the infected host. In the present study we investigated the effect of benznidazole therapy on the lymphoid compartment during the course of experimental T. cruzi infection. Although amelioration of a variety of clinical and parasitological signs was observed in treated mice, amelioration of splenocyte expansion was not detected. Interestingly, this sustained splenomegaly observed in benznidazole-treated mice showed a preferential expansion of CD8+ T lymphocytes. Moreover, although benznidazole treatment blocked the expansion of recently activated CD4+ and CD8+ T cells seen in infected hosts, benznidazole treatment led to a selective expansion of effector and memory CD8+ T lymphocytes in association with a lower rate of apoptosis. In addition, the surviving treated animals were protected from reinfection. Together, these data suggest that, in addition to its well-known direct role in blocking parasite replication in vivo, benznidazole appears to directly affect immune regulation in T. cruzi-infected hosts.

Specific features of T- and NK-cellular immunity in chronic lymphocytic leukemia

2021 ◽  
Vol 66 (6) ◽  
pp. 345-352
Author(s):  
Evgeniy Vladimirovich Pochtar ◽  
S. A. Lugovskaya ◽  
E. V. Naumova ◽  
E. A. Dmitrieva ◽  
A. I. Kostin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Lymphocytic Leukemia ◽  
Positive Trend ◽  
Functional Changes ◽  
Activated T Lymphocytes ◽  
T Helpers

Profound immunological dysfunction is the key factor determining the development of infectious complications in chronic lymphocytic leukemia (CLL). The aim of this work is to assess the features of the subpopulation composition of T-lymphocytes (T-helpers (Th), cytotoxic T-lymphocytes (Tcyt), T regulatory cells (Treg), T-NK cells, naive Th, Th-memory, activated T-lymphocytes, TCRγδ cells) and NK cells in peripheral blood of patients with newly diagnosed chronic lymphocytic leukemia (CLL) and receiving ibrutinib therapy. Hematological and immunophenotypic studies have been performed in 30 patients with previously untreated CLL, 122 patients on ibrutinib therapy and 20 healthy donors. The subpopulation composition of T-lymphocytes (Th, Tcyt, Treg, T-NK, naive T-helpers, memory T-helpers, TCRγδ cells, activated T-lymphocytes) and NK cells has been assessed on flow cytometer (FACSCanto II (BD)) using the following panel of monoclonal antibodies: CD45, CD19, CD3, CD4, CD5, CD8, TCRγδ, CD127, CD16, CD56, CD57 CD45RA, CD45R0, HLA-DR, CD25. Compared to controls all CLL samples were found to have higher the absolute number of T-lymphocytes, NK cells and their subpopulations, T-helpers (especially of memory T-cells), cytotoxic T-cells, regulatory T-cells, TCRγδ T-cells, activated T-lymphocytes, increased cytotoxic potential of NK cells in previously untreated CLL patients. Patients who received ibrutinib therapy have registered a positive trend towards recovery of the subpopulation composition of T-lymphocytes and NK-cells. CLL patients have been found to have quantitative and functional changes in the subpopulations of T-lymphocytes and NK cells, indicating dysregulation of the immune response, and a high risk of developing infections. Monitoring of immunological parameters for ibrutinib therapy make possible to estimate impact of ibrutinib on the adaptive anti-CLL immune response.

scholarly journals Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity

2018 ◽  
Vol 9 ◽  
Author(s):  
Cintia L. Araujo Furlan ◽  
Jimena Tosello Boari ◽  
Constanza Rodriguez ◽  
Fernando P. Canale ◽  
Facundo Fiocca Vernengo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Trypanosoma Cruzi ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cell Immunity ◽  
Cruzi Infection

scholarly journals Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium

2005 ◽  
Vol 389 (2) ◽  
pp. 527-539 ◽  
Author(s):  
Shasi V. Kalivendi ◽  
Eugene A. Konorev ◽  
Sonya Cunningham ◽  
Sravan K. Vanamala ◽  
Eugene H. Kaji ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Lymphocytes ◽  
Fas Ligand ◽  
Reactive Oxygen ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Rat Cardiomyocytes ◽  
Activated T Lymphocytes ◽  
Pre Treatment ◽  
Fas L

Doxorubicin (DOX), a widely used antitumour drug, causes dose-dependent cardiotoxicity. Cardiac mitochondria represent a critical target organelle of toxicity during DOX chemotherapy. Proposed mechanisms include generation of ROS (reactive oxygen species) and disturbances in mitochondrial calcium homoeostasis. In the present study, we probed the mechanistic link between mitochondrial ROS and calcium in the embryonic rat heart-derived H9c2 cell line and in adult rat cardiomyocytes. The results show that DOX stimulates calcium/calcineurin-dependent activation of the transcription factor NFAT (nuclear factor of activated T-lymphocytes). Pre-treatment of cells with an intracellular calcium chelator abrogated DOX-induced nuclear NFAT translocation, Fas L (Fas ligand) expression and caspase activation, as did pre-treatment of cells with a mitochondria-targeted antioxidant, Mito-Q (a mitochondria-targeted antioxidant consisting of a mixture of mitoquinol and mitoquinone), or with adenoviral-over-expressed antioxidant enzymes. Treatment with GPx-1 (glutathione peroxidase 1), MnSOD (manganese superoxide dismutase) or a peptide inhibitor of NFAT also inhibited DOX-induced nuclear NFAT translocation. Pre-treatment of cells with a Fas L neutralizing antibody abrogated DOX-induced caspase-8- and -3-like activities during the initial stages of apoptosis. We conclude that mitochondria-derived ROS and calcium play a key role in stimulating DOX-induced ‘intrinsic and extrinsic forms’ of apoptosis in cardiac cells with Fas L expression via the NFAT signalling mechanism. Implications of ROS- and calcium-dependent NFAT signalling in DOX-induced apoptosis are discussed.

scholarly journals Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells.

1990 ◽  
Vol 172 (6) ◽  
pp. 1873-1876 ◽  
Author(s):  
S Scott ◽  
F Pandolfi ◽  
J T Kurnick
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Lymphocytes ◽  
Cell Survival ◽  
Conditioned Medium ◽  
Stromal Cell ◽  
Interleukin 2 ◽  
Salvage Pathway ◽  
Activated T Lymphocytes ◽  
T Cell Survival

This report describes a salvage pathway whereby activated T lymphocytes revert to nonproliferating cells in the absence of antigen or mitogenic signals. After the removal of mitogenic cytokines, cultured T lymphocytes cease dividing and rapidly begin to undergo cell death. However, the addition of fibroblasts to interleukin 2 (IL-2)-propagated T cells results in prolonged survival of the previously activated T lymphocytes in the absence of proliferation. The prevention of cell death is also achieved by conditioned medium from the fibroblasts. T lymphocytes cultured with fibroblasts or the conditioned medium retain the ability to be restimulated if mitogenic stimuli are added to the culture. The activity is not accounted for by IL-1-7. The studies suggest a stromal cell-mediated, nonspecific mechanism for survival of primed T lymphocytes in a nonproliferating state.

scholarly journals A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Adriana Egui ◽  
M. Carmen Thomas ◽  
Ana Fernández-Villegas ◽  
Elena Pérez-Antón ◽  
Inmaculada Gómez ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Drastic Reduction ◽  
Content Type ◽  
Short Period ◽  
Before And After ◽  
Cruzi Infection

ABSTRACT One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B+/perforin+ CD8+ T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P < 0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8+ T cells compared with that in the patients who did not meet the STEC.

T lymphocyte proliferative capacity and CD4+/CD8+ ratio in primiparous and pluriparous lactating cows

2008 ◽  
Vol 75 (4) ◽  
pp. 457-465 ◽  
Author(s):  
Jalil Mehrzad ◽  
Xin Zhao
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Dairy Cows ◽  
T Lymphocyte ◽  
Farm Animals ◽  
T Lymphocyte Subsets ◽  
Lactating Cows ◽  
Proliferation Capacity ◽  
First Time ◽  
Increased Susceptibility

T cells play a central role in specific immunity; their populations and phenotypes could be affected by number of lactation in high-yielding dairy cows. To investigate the effects of parity on the dynamics of T lymphocytes, lymphoproliferative capacity, T lymphocyte subsets and CD4+/CD8+ ratio were studied in peripheral blood of primiparous and pluriparous dairy cows during mid–late lactation. A non-radioactive technique was also adapted for a detailed lymphoproliferation assay. Compared with the primiparous cows, the pluriparous cows exhibited weaker lymphoproliferative activity, larger number of CD4+ cells and substantially greater CD4+/CD8+ ratio in their blood circulation. The increase of the CD4+/CD8+ ratio in the blood of pluriparous dairy cows was mainly due to the rise in the proportion of CD4+ cells and decline in the proportion of CD8+ cells. This increase of the CD4+/CD8+ ratio coincided with the decrease of mitogen-induced proliferation capacity of T lymphocytes. Of four lymphocyte divisions or generations during the lymphoproliferation assay, maximal lymphocyte proliferation capacity at generation 3 in primiparous cows was markedly greater than in pluriparous cows. With an alternatively safer, faster and more reproducible assay (compared with 3H-thymidine scintillation assay) we showed for the first time that aging in dairy cows leads to a decreased mitogen-induced lymphoproliferation and disturbed proportion between CD4+ and CD8+ T cells. This CD4+-CD8+ imbalance together with diminished lymphoproliferative capacity may lead to a weaker T cytotoxic-mediated immunity and increased susceptibility to infectious diseases in pluriparous lactating cows. Our study also emphasizes further application of the methods in farm animals.

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