scholarly journals Importance of T Lymphocytes in Brain Injury, Immunodeficiency, and Recovery after Cerebral Ischemia

2012 ◽  
Vol 32 (4) ◽  
pp. 598-611 ◽  
Author(s):  
Vanessa H Brait ◽  
Thiruma V Arumugam ◽  
Grant R Drummond ◽  
Christopher G Sobey
Keyword(s):  
Brain Injury ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
Infectious Complications ◽  
Increased Risk ◽  
The Hours ◽  
Immunodeficiency Syndrome ◽  
Subsets Of T Lymphocytes ◽  
The Brain

Following an ischemic stroke, T lymphocytes become activated, infiltrate the brain, and appear to release cytokines and reactive oxygen species to contribute to early inflammation and brain injury. However, some subsets of T lymphocytes may be beneficial even in the early stages after a stroke, and recent evidence suggests that T lymphocytes can also contribute to the repair and regeneration of the brain at later stages. In the hours to days after stroke, T-lymphocyte numbers are then reduced in the blood and in secondary lymphoid organs as part of a ‘stroke-induced immunodeficiency syndrome,’ which is mediated by hyperactivity of the sympathetic nervous system and the hypothalamic—pituitary—adrenal axis, resulting in increased risk of infectious complications. Whether or not poststroke T-lymphocyte activation occurs via an antigen-independent process, as opposed to a classical antigen-dependent process, is still controversial. Although considerable recent progress has been made, a better understanding of the roles of the different T-lymphocyte subpopulations and their temporal profile of damage versus repair will help to clarify whether T-lymphocyte targeting may be a viable poststroke therapy for clinical use.

scholarly journals Central Nervous System-Infiltrating T Lymphocytes in Stroke Are Activated via Their TCR (T-Cell Receptor) but Lack CD25 Expression

Stroke ◽  
2021 ◽  
Author(s):  
Juliane Schulze ◽  
Juliane Gellrich ◽  
Michael Kirsch ◽  
Alexander Dressel ◽  
Antje Vogelgesang
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Fluorescent Protein ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Artery Occlusion ◽  
Cd25 Expression ◽  
The Brain

Background and Purpose: T lymphocytes contribute to secondary brain damage after stroke. It has not been fully investigated whether this contribution is caused by antigen-specific or antigen-nonspecific activation of T lymphocytes. Lymphocytes from Nur77 GFP transgenic mice express a fluorescent protein upon activation via the TCR (T-cell receptor), allowing the differentiation of activation mode in a natural repertoire of immune cells and antigens. Methods: Middle cerebral artery occlusion or sham surgery was performed, and T-lymphocyte activation was analyzed by flow cytometry in the brain, spleen, and blood 16 hours, 2 days, 3 days, 4 days, and 7 days after surgery. Results: Ipsilateral hemispheric T-lymphocyte invasion peaked on day 4 poststroke. Here, we observed PD-1 (programmed cell death protein 1) expression on almost all invading T lymphocytes, while CD25 expression was low. CD25+, CD69+, or PD-1+ T lymphocytes predominantly displayed antigen-specific activation; the opposite was observed for T lymphocytes isolated from the blood. A mixed activation that favored antigen-specific activation was observed in the spleen. PD-1 was upregulated within the brain, whereas CD25 was not. Antigen-specific T lymphocytes home to the brain, while antigen- nonspecifically activated cells remain within the blood. Conclusions: Our data clearly demonstrate antigen-specific activation of T lymphocytes infiltrating ischemic brain lesions in stroke. The high expression of inhibitory PD-1 and low expression of CD25 on activated T lymphocytes in the brain most likely reflect immunosuppressive mechanisms.

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 Sport-related concussions

2014 ◽  
Vol 8 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Jéssica Natuline Ianof ◽  
Fabio Rios Freire ◽  
Vanessa Tomé Gonçalves Calado ◽  
Juliana Rhein Lacerda ◽  
Fernanda Coelho ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Changes ◽  
American Football ◽  
Health Concern ◽  
Public Health Concern ◽  
Increased Risk ◽  
High Prevalence ◽  
Biomechanical Forces ◽  
The Brain

ABSTRACT Traumatic brain injury (TBI) is a major cause of lifelong disability and death worldwide. Sport-related traumatic brain injury is an important public health concern. The purpose of this review was to highlight the importance of sport-related concussions. Concussion refers to a transient alteration in consciousness induced by external biomechanical forces transmitted directly or indirectly to the brain. It is a common, although most likely underreported, condition. Contact sports such as American football, rugby, soccer, boxing, basketball and hockey are associated with a relatively high prevalence of concussion. Various factors may be associated with a greater risk of sport-related concussion, such as age, sex, sport played, level of sport played and equipment used. Physical complaints (headache, fatigue, dizziness), behavioral changes (depression, anxiety, irritability) and cognitive impairment are very common after a concussion. The risk of premature return to activities includes the prolongation of post-concussive symptoms and increased risk of concussion recurrence.

scholarly journals Vancomycin Is Protective in a Neonatal Mouse Model of Staphylococcus epidermidis-Potentiated Hypoxic-Ischemic Brain Injury

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Jacqueline C. Y. Lai ◽  
Pernilla Svedin ◽  
C. Joakim Ek ◽  
Amin Mottahedin ◽  
Xiaoyang Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Mouse Model ◽  
Preterm Infants ◽  
Staphylococcus Epidermidis ◽  
Neonatal Mouse ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Brain ◽  
Content Type ◽  
Increased Risk ◽  
The Brain

ABSTRACT Infection is correlated with increased risk of neurodevelopmental sequelae in preterm infants. In modeling neonatal brain injury, Toll-like receptor agonists have often been used to mimic infections and induce inflammation. Using the most common cause of bacteremia in preterm infants, Staphylococcus epidermidis, we present a more clinically relevant neonatal mouse model that addresses the combined effects of bacterial infection together with subsequent hypoxic-ischemic brain insult. Currently, there is no neuroprotective treatment for the preterm population. Hence, we tested the neuroprotective effects of vancomycin with and without adjunct therapy using the anti-inflammatory agent pentoxifylline. We characterized the effects of S. epidermidis infection on the inflammatory response in the periphery and the brain, as well as the physiological changes in the central nervous system that might affect neurodevelopmental outcomes. Intraperitoneal injection of postnatal day 4 mice with a live clinical isolate of S. epidermidis led to bacteremia and induction of proinflammatory cytokines in the blood, as well as transient elevations of neutrophil and monocyte chemotactic cytokines and caspase 3 activity in the brain. When hypoxia-ischemia was induced postinfection, more severe brain damage was observed in infected animals than in saline-injected controls. This infection-induced inflammation and potentiated brain injury was inoculum dose dependent and was alleviated by the antibiotic vancomycin. Pentoxifylline did not provide any additional neuroprotective effect. Thus, we show for the first time that live S. epidermidis potentiates hypoxic-ischemic preterm brain injury and that peripheral inhibition of inflammation with antibiotics, such as vancomycin, reduces the extent of brain injury.

Impaired T-Lymphocyte Subpopulations and Deranged Profile of Immunologic Activation in Patients with Gaucher Disease Type I

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4915-4915
Author(s):  
Argiris S Symeonidis ◽  
George Theodorou ◽  
Constantina Repa ◽  
Theodore Marinakis ◽  
Panayiotis Tsaftaridis ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Gaucher Disease ◽  
Lymphocyte Activation ◽  
Absolute Number ◽  
Lymphocyte Subpopulations ◽  
Type I ◽  
Cd8 T Lymphocytes ◽  
T Lymphocyte Subpopulations ◽  
Hla Dr

Abstract Patients with Gaucher disease exhibit substantial evidence of impairment of their immune system, namely, increased serum levels of proinflammatory cytokines and immunoglobulins, and increased incidence of B-cell malignancies, such as non-Hodgkin’s lymphoma, MGUS and multiple myeloma. We investigated peripheral blood T-lymphocyte subpopulations with dual color flow cytometry, as well as the direction of T-lymphocyte activation, by using intracytoplasmic immunostaining for IL-2, IL-4, IL-10 and IFN-gamma, on resting CD4+ and CD8+ T-lymphocytes and following activation with PMA- 1 with the presence of Brefeldin-A. Evaluations were performed on 16 patients with type I Gaucher disease and on 17 healthy controls. Patients had significantly decreased absolute lymphocyte count (1621±684 vs 2148±566/mm3, p=0.013), CD3+ (1197±478 vs 1508±431/mm3, p=0.045) and CD4+ T-lymphocytes (658±245 vs 945±253/mm3, p=0.021), but not CD8+ T-lymphocytes (491±331 vs 486±189/mm3, p: n.s.), resulting in a significant reduction of the CD4/CD8 ratio (1.59±0.68 vs 2.16±0.83, p=0.041). The populations of naive CD4+CD45RA+ and of memory CD4+CD45RO+ T-lymphocytes were also significantly decreased (218±128 vs 432±179/mm3, p=0.0005 and 484±185 vs 631±231/mm3, p=0.056 respectively), however, CD8+CD45RA+ and CD8+CD45RO+ subpopulations did nor differ significantly, when compared to controls. CD3−CD56+, but not CD3+CD56+ lymphocytes were also decreased (131±82 vs 199±97/mm3, p=0.037). Patients had higher percentages of CD8+ (29.2±9.7 vs 23.5±6.8%, p=0.042), CD8+CD45RA+ (22.1±6.2 vs 18.3±5.0%, p=0.046) and CD8+CD45RO+ T-lymphocytes (13.2±6.2 vs 9.6±3.7%, p=0.027), as well as of activated CD8+HLA-DR+ (0.93±0.68 vs 0.48±0.21%, p=0.008) and CD4+HLA-DR+ T-lymphocytes (1.77±0.93 vs 1.09±0.48%, p=0.008). Moreover, although both, the absolute number and the percentage of CD20+ B-lymphocytes were similar, patients exhibited significantly increased absolute number and percentage of CD5+CD20+ B-lymphocytes (1.63±0.55 vs 0.64±0.37% p=0.00002 and 29±20 vs 13±8/mm3, p=0.011, respectively). Finally, patients with Gaucher disease had significantly increased resting TH2-polarized CD4+T-lymphocytes (CD4+IL-10+: 0.41±0.29 vs 0.24±0.11%, p=0.045) and TH1-polarized CD8+ T-lymphocytes (CD8+IFNγ+: 0.15±0.07 vs 0.08±0.04%, p=0.005, CD8+IL10+: 0.22±0.08 vs 0.32±0.014, p=0.052, and IFNγ+/IL4+ ratio among the CD8+ population 2.54±2.1 vs 1.08±0.91, p=0.018). Following mitogenic activation a very significant impairment of obtaining the TH1 phenotype was observed (CD4+IL2+ lymphocytes 33.7±17.1 vs 65.4±6.1%, p<0.00001). The above findings suggest that in patients with Gaucher disease there is a significant numerical impairment of T-helper lymphocytes and a shift towards TH-2 direction of lymphocyte activation. These findings may explain the rarity of autoimmune manifestations despite the chronic inflammatory reaction, as well as the increased incidence of lymphoid malignancies, which has been reported among patients suffering from this disease.

scholarly journals Immune cell populations in cutaneous delayed-type hypersensitivity.

1983 ◽  
Vol 158 (4) ◽  
pp. 1227-1242 ◽  
Author(s):  
J L Platt ◽  
B W Grant ◽  
A A Eddy ◽  
A F Michael
Keyword(s):  
Monoclonal Antibodies ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Lymphocyte Activation ◽  
Delayed Type Hypersensitivity ◽  
Cell Populations ◽  
T Lymphocyte Activation ◽  
Cutaneous Response ◽  
Leu 7

Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte-mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of the OKT4 subpopulation of T lymphocytes in tissue infiltrates and subsequent (15-48 h) evidence of T lymphocyte activation.

Gangliosides and glycophorin inhibit T-lymphocyte activation

1990 ◽  
Vol 68 (4) ◽  
pp. 735-744 ◽  
Author(s):  
Frances J. Sharom ◽  
Anita L. H. Chiu ◽  
T. Elaine Ross
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Bovine Brain ◽  
Inhibition Of Proliferation ◽  
Mechanism Of Inhibition ◽  
Dependent Cell ◽  
Brain Gangliosides

Increased levels of gangliosides in the serum have been linked to tumour-induced immunosuppression in vivo. Both bovine brain gangliosides and human erythrocyte glycophorin were potent inhibitors of concanavalin A, periodate, and phorbol ester – ionomycin induced activation of murine T-lymphocytes. Structurally complex gangliosides were more inhibitory, while simpler glycolipids caused less inhibition. Lymphocytes exposed to these molecules for up to 24 h could still proliferate after washing. Substantial inhibition was observed only when gangliosides and glycophorin were present during the first 18 h of activation. Studies using Quin-2 showed that gangliosides did not block the initial rapid rise in cytoplasmic Ca2+ following mitogen stimulation. Interleukin-2 (IL-2) production by ganglioside- and glycophorin-treated lymphocytes was unchanged. After treatment with gangliosides for 24 h, lymphocytes proliferated normally in response to added IL-2. These results suggest that the first round of signal transduction in response to mitogen was unaffected by gangliosides. Addition of gangliosides to activated lymphocytes in the presence of IL-2 resulted in complete inhibition of proliferation. Immunosuppression by gangliosides and glycophorin thus appears to occur at the IL-2-dependent stage of proliferation and may be partially due to IL-2 binding to these molecules. However, high levels of IL-2 failed to reverse inhibition and IL-2-dependent cell lines were much less sensitive to ganglioside inhibition than T-lymphocytes, suggesting that more than one mechanism of inhibition likely exists.Key words: gangliosides, glycophorin, T-lymphocyte, interleukin-2, interleukin-2 receptor.

scholarly journals Alternative pathways of T lymphocyte activation.

1978 ◽  
Vol 148 (3) ◽  
pp. 829-834 ◽  
Author(s):  
F H Bach ◽  
B J Alter
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Significant Role ◽  
Lymphocyte Activation ◽  
Alternative Pathways ◽  
Cytotoxic Response ◽  
Helper T Lymphocytes ◽  
D Region

Data presented in this paper suggest that there may be two alternative pathways which T lymphocytes can use in generating a cytotoxic response to alloantigens in vitro. First, there is the pathway taken when stimulator and responder cells differ by an entire H-2 complex where Ly1+2- helper T lymphocytes respond to I region encoded lymphocyte defined differences and provide help to the Ly1-2+ cytotoxic T lymphocytes responsive primarily to K/D region encoded cytotoxicity defined determinants. Second, there is the pathway taken when stimulator and responder cells differ by only K or D region differences without an I region encoded difference; under these conditions, an Ly1+2+ cell, which does not appear to play a significant role in the development of a cytotoxic response to an entire H-2 difference, appears to play a pivotal role.

scholarly journals Therapeutic Dilemmas regarding Anticoagulation: An Experience in a Patient with Nephrotic Syndrome, Pulmonary Embolism, and Traumatic Brain Injury

2016 ◽  
Vol 9 ◽  
pp. CCRep.S40607 ◽  
Author(s):  
Tetsu Akimoto ◽  
Tomoyuki Yamazaki ◽  
Eiji Kusano ◽  
Daisuke Nagata
Keyword(s):  
Traumatic Brain Injury ◽  
Pulmonary Embolism ◽  
Nephrotic Syndrome ◽  
Brain Injury ◽  
Bleeding Complications ◽  
Brain Contusion ◽  
Increased Risk ◽  
Substantial Risk ◽  
The Brain ◽  
Acute Pe

Patients with active bleeding complications who concomitantly develop overt pulmonary embolism (PE) present distinct therapeutic dilemmas, since they are perceived to be at substantial risk for the progression of the embolism in the absence of treatment and for aggravation of the hemorrhagic lesions if treated with anticoagulants. A 76-year-old patient with nephrotic syndrome, which is associated with an increased risk of thromboembolism, concurrently developed acute PE and intracranial bleeding because of traumatic brain injury. In this case, we prioritized the treatment for PE with the intravenous unfractionated heparin followed by warfarinization. Despite the transient hemorrhagic progression of the brain contusion after the institution of anticoagulation, our patient recovered favorably from the disease without any signs of neurological compromise. Several conundrums regarding anticoagulation that emerged in this case are also discussed.

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