T Lymphocytes: The “Cellular” Arm of Acquired Immunity in the Peritoneum

2006 ◽  
Vol 26 (4) ◽  
pp. 438-448 ◽  
Author(s):  
Amir Glik ◽  
Amos Douvdevani
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Antigen Presentation ◽  
Cell Population ◽  
Cell Biology ◽  
Specific Antigen ◽  
Acquired Immunity ◽  
Polymorphonuclear Cells

T cells are an important part of the acquired immune response and target specific antigen with their T cell receptor. The peritoneum is a special milieu within which T cells react. We describe briefly the anatomy important for T cell function. T cell biology including antigen presentation, T cell activation, and the different T cell subpopulations are reviewed. We also define innate and acquired immunity and describe the role of polymorphonuclear cells and peritoneal mesothelial cells in the regulation of leukocyte population recruitment during peritonitis. We focus particularly on peritoneal lymphocytes and compare them to the regular lymphocyte populations in the circulation. We illustrate the role of PMCs in antigen presentation and discuss the changes of CD4+ helper T cell subtypes (Th1 and Th2) during peritoneal dialysis. The role of CD8+ cytotoxic T lymphocytes and their possible destructive role for the peritoneal membrane modified by advanced glycation end products are discussed. Polymorphonuclear cells play an important role in the regulation of inflammation and immunity. We describe their possible role in supporting T cells and particularly for generating memory CD8+ T cells by secretion of interleukin-15, a potent T cell growth factor. Light is shed on γδ T cells, a special T cell population that is able to recognize antigens without the restriction of antigen presentation. We end our review with a description of regulatory T cells. This cell population is extremely important in preventing autoimmunity and in the regulation of acquired immunity.

scholarly journals Isolevuglandin-Modified Cardiac Proteins Drive CD4+ T Cell Activation in the Heart and Promote Cardiac Dysfunction

Circulation ◽  
2021 ◽  
Author(s):  
Njabulo Ngwenyama ◽  
Annet Kirabo ◽  
Mark Aronovitz ◽  
Francisco Velázquez ◽  
Francisco Carrillo-Salinas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cardiac Dysfunction ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Myocardial Oxidative Stress

Background: Despite the well-established association between T cell-mediated inflammation and non-ischemic heart failure (HF), the specific mechanisms triggering T cell activation during the progression of HF and the antigens involved are poorly understood. We hypothesized that myocardial oxidative stress induces the formation of isolevuglandin (IsoLG)-modified proteins that function as cardiac neoantigens to elicit CD4+ T cell receptor (TCR) activation and promote HF. Methods: We used transverse aortic constriction (TAC) in mice to trigger myocardial oxidative stress and T cell infiltration. We profiled the TCR repertoire by mRNA sequencing of intramyocardial activated CD4+ T cells in Nur77 GFP reporter mice, which transiently express GFP upon TCR engagement. We assessed the role of antigen presentation and TCR specificity in the development of cardiac dysfunction using antigen presentation-deficient MhcII -/- mice, and TCR transgenic OTII mice that lack specificity for endogenous antigens. We detected IsoLG-protein adducts in failing human hearts. We also evaluated the role of reactive oxygen species (ROS) and IsoLGs in eliciting T cell immune responses in vivo by treating mice with the antioxidant TEMPOL, and the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) during TAC, and ex-vivo in mechanistic studies of CD4+ T cell proliferation in response to IsoLG-modified cardiac proteins. Results: We discovered that TCR antigen recognition increases in the left ventricle (LV) as cardiac dysfunction progresses, and identified a limited repertoire of activated CD4+ T cell clonotypes in the LV. Antigen presentation of endogenous antigens was required to develop cardiac dysfunction since MhcII -/- mice reconstituted with CD4+ T cells, and OTII mice immunized with their cognate antigen were protected from TAC-induced cardiac dysfunction despite the presence of LV-infiltrated CD4+ T cells. Scavenging IsoLGs with 2-HOBA reduced TCR activation and prevented cardiac dysfunction. Mechanistically, cardiac pressure overload resulted in ROS dependent dendritic cell accumulation of IsoLG-protein adducts which induced robust CD4+ T cell proliferation. Conclusions: Collectively, our study demonstrates an important role of ROS-induced formation of IsoLG-modified cardiac neoantigens that lead to TCR-dependent CD4+ T cell activation within the heart.

scholarly journals T Cell Receptor Specificity Is Critical for the Development of Epidermal γδ T Cells

2001 ◽  
Vol 194 (10) ◽  
pp. 1473-1483 ◽  
Author(s):  
Isabel Ferrero ◽  
Anne Wilson ◽  
Friedrich Beermann ◽  
Werner Held ◽  
H. Robson MacDonald
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Biology ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Wild Type ◽  
Normal Numbers ◽  
T Cell Biology

A particular feature of γδ T cell biology is that cells expressing T cell receptor (TCR) using specific Vγ/Vδ segments are localized in distinct epithelial sites, e.g., in mouse epidermis nearly all γδ T cells express Vγ3/Vδ1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal Vγ3+ thymocytes. The role of γδ TCR specificity in DETC's migration/localization to the skin has remained controversial. To address this issue we have generated transgenic (Tg) mice expressing a TCR δ chain (Vδ6.3-Dδ1-Dδ2-Jδ1-Cδ), which can pair with Vγ3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) Vδ6.3Tg mice DETC were present and virtually all of them express Vδ6.3. However, DETC were absent in TCR-δ−/− Vδ6.3Tg mice, despite the fact that Vδ6.3Tg γδ T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt Vδ6.3Tg mice, a high proportion of in-frame Vδ1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR-δ (most probably Vδ1) was required for the development of Vδ6.3+ epidermal γδ T cells. Collectively our data demonstrate that TCR specificity is essential for the development of γδ T cells in the epidermis. Moreover, they show that the TCR-δ locus is not allelically excluded.

Interferon- Activates Multiple STAT Proteins and Upregulates Proliferation-Associated IL-2R, c-myc, and pim-1 Genes in Human T Cells

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 1980-1991 ◽  
Author(s):  
Sampsa Matikainen ◽  
Timo Sareneva ◽  
Tapani Ronni ◽  
Anne Lehtonen ◽  
Päivi J. Koskinen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Biology ◽  
Interleukin 2 ◽  
T Cell Proliferation ◽  
Stat Proteins ◽  
Human T Cells ◽  
T Cell Biology ◽  
Cytokine Stimulation

Interferon- (IFN-) is a pleiotropic cytokine that has antiviral, antiproliferative, and immunoregulatory functions. There is increasing evidence that IFN- has an important role in T-cell biology. We have analyzed the expression ofIL-2R, c-myc, and pim-1 genes in anti-CD3–activated human T lymphocytes. The induction of these genes is associated with interleukin-2 (IL-2)–induced T-cell proliferation. Treatment of T lymphocytes with IFN-, IL-2, IL-12, and IL-15 upregulated IL-2R, c-myc, andpim-1 gene expression. IFN- also sensitized T cells to IL-2–induced proliferation, further suggesting that IFN- may be involved in the regulation of T-cell mitogenesis. When we analyzed the nature of STAT proteins capable of binding to IL-2R,pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN-–induced binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements. Yet, IFN- was able to activate binding of STAT5 to the high-affinity IFP53 GAS site. IFN- enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a, and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements. Taken together, our results suggest that IFN-, IL-2, IL-12, and IL-15 have overlapping activities on human T cells. These findings thus emphasize the importance of IFN- as a T-cell regulatory cytokine.

An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Graziella Curtale ◽  
Franca Citarella ◽  
Claudia Carissimi ◽  
Marina Goldoni ◽  
Nicoletta Carucci ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Activation Induced Cell Death

Abstract Activation of the T cell–mediated immune response has been associated with changes in the expression of specific microRNAs (miRNAs). However, the role of miRNAs in the development of an effective immune response is just beginning to be explored. This study focuses on the functional role of miR-146a in T lymphocyte–mediated immune response and provides interesting clues on the transcriptional regulation of miR-146a during T-cell activation. We show that miR-146a is low in human naive T cells and is abundantly expressed in human memory T cells; consistently, miR-146a is induced in human primary T lymphocytes upon T-cell receptor (TCR) stimulation. Moreover, we identified NF-kB and c-ETS binding sites as required for the induction of miR-146a transcription upon TCR engagement. Our results demonstrate that several signaling pathways, other than inflammation, are influenced by miR-146a. In particular, we provide experimental evidence that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR-146a. Furthermore, miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity.

scholarly journals Potensi Curcumin dan 4 Herbal Empon-Empon Dalam Memodulasi Kekebalan Sel T Terhadap Covid-19

2021 ◽  
Vol 4 (3) ◽  
pp. 72
Author(s):  
Aryo Tedjo ◽  
Dimas Noor ◽  
Rudi Heryanto
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Function ◽  
Cellular Responses ◽  
Herbal Extracts ◽  
Memory T Cell ◽  
Cell Counts ◽  
Compound Database

Longer immunity to Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection is thought to occur through memory cellular responses by activity of specific T lymphocytes. However, most patients with Coronavirus disease-19 (Covid-19) experienced a decrease in the number of T lymphocytes or lymphopenia. Agents that help maintain T cell counts such as Curcumin appear to have played an important role during the Covid-19 pandemic. Curcumin is known to provide a balance between T cell effectiveness and T cell autoaggressiveness, as well as restoring memory T cell function as observed in tumor-induced mice. The mixture of 4 herbal extracts of empon-empon which is commonly used as herbal medicine, namely temulawak, ginger, lemongrass, and turmeric, is thought to have the same effect as curcumin. This is known from the tracing of a plant-protein-compound database which shows that there are not many compounds other than curcumin that can modulate T cells. It is necessary to study the role of Curcumin and a mixture of 4 herbal empon-empon in modulating T cells in cases of infection by the SARS-Cov-2 antigen.

scholarly journals Increase in inflammatory T cell subsets in atrial fibrillation: the missing link underlying inflammation in AF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.E Dumitriu ◽  
P Dimou ◽  
S Kaur ◽  
S Dinkla ◽  
J.C Kaski ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Inflammatory Cytokines ◽  
T Lymphocyte ◽  
Treg Cells ◽  
Funding Source ◽  
Functional Assays

Abstract Background The precise role of inflammation in the development and perpetuation of atrial fibrillation (AF) is yet to be fully uncovered. T lymphocytes have pivotal roles in orchestrating inflammation. Specialised subsets of lymphocytes either promote or prevent inflammation. We are investigating a unique subset of lymphocytes, the CD4+CD28null T cells that expand in patients with chronic inflammation. These cells secrete high levels of pro-inflammatory cytokines and have cytolytic function. CD4+CD28null T cells are normally maintained under control by regulatory T cells (Treg), a specialised subset of T lymphocytes with suppressive function that maintain immune homeostasis and prevent pathogenic immune responses. The role of CD4+CD28null and Treg cells has not been investigated in AF. Purpose We hypothesised that in AF the balance between pro-inflammatory and regulatory T lymphocytes is skewed in favour of inflammatory T cells, which may sustain inflammation in AF. Methods Circulating CD4+CD28null T lymphocytes and Tregs were quantified by flow cytometry in paroxysmal and persistent AF patients and healthy controls (n=30). Inflammatory cytokines were quantified in serum and the function of T lymphocyte subsets was investigated using ex vivo functional assays. Results CD4+CD28null T lymphocytes were significantly increased in the circulation of AF patients compared to controls. Of note, a higher proportion of patients with persistent AF showed an increase in inflammatory CD4+CD28null T lymphocytes compared to patients with paroxysmal AF. A marked reduction in Treg cells was present in AF patients compared to controls. Functional assays showed that IL-7 and IL-15 cytokines were responsible for CD4+CD28null T lymphocyte expansion in AF patients. Conclusions We show that patients with AF have marked changes in T lymphocytes subsets: pro-inflammatory CD4+CD28null T cells increase significantly, whilst anti-inflammatory Tregs are significantly reduced. We show for the first time that the cytokines IL-7 and IL-15 are the main drivers of CD4+CD28null T cell expansion in AF patients. These novel findings may reveal novel therapeutic strategies (e.g. cytokine blockade) to re-establish the balance between pro- and anti-inflammatory mechanisms at work in AF to improve patient outcomes. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Coordinate expression and proliferative role of HOXB genes in activated adult T lymphocytes

1994 ◽  
Vol 14 (7) ◽  
pp. 4872-4877
Author(s):  
A Carè ◽  
U Testa ◽  
A Bassani ◽  
E Tritarelli ◽  
E Montesoro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Retinoic Acid ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Rnase Protection ◽  
Activated T Lymphocytes

We investigated the expression of HOXB cluster genes in purified phytohemagglutinin (PHA)-activated T lymphocytes from normal adult peripheral blood by reverse transcription PCR and RNase protection. These genes are not expressed in quiescent T cells, except for barely detectable B1 RNA. After the PHA stimulus, HOXB gene activation initiates coordinately as a rapid induction wave in the 3'-->5' cluster direction (i.e., from HOXB1 through B9 genes). Thus, (i) expression of the foremost 3'-located B1 and B2 genes peaks 10 min after PHA addition and then rapidly declines, (ii) activation of B3, B4, and B5 begins 10 min after PHA addition and peaks at later times (i.e., at 120 min for B5), (iii) B6, B7, and B9 are expressed at a low level starting at later times (45 to 60 min), and (iv) B8 remains silent. Treatment of PHA-activated T lymphocytes with antisense oligonucleotides to B2 or B4 mRNA causes a drastic inhibition of T-cell proliferation and a decreased expression of T-cell activation markers (i.e., interleukin 2 and transferrin receptors). Similarly, treatment of CEM-CCRF, Peer, and SEZ627 T acute lymphocytic leukemia cell lines with anti-B4 oligomer markedly inhibits cell proliferation. Finally, T cells stimulated by a low dosage of PHA in the presence of 1 microM retinoic acid show a marked increase of both HOXB expression, particularly B2, and cell proliferation. These studies provide novel evidence on the role of HOX genes in adult cell proliferation. (i) Coordinate, early activation of HOXB genes from the 3'-->5' cluster side apparently underlies T-cell activation. (ii) The expression pattern in adult PHA-activated T cells is strikingly similar to that observed in retinoic acid-induced teratocarcinoma cells (A. Simeone, D. Acampora, L. Arcioni, P. W. Andres, E. Boncinelli, and F. Mavilio, Nature (London) 346:763-766, 1990), thus suggesting that molecular mechanisms underlying HOX gene expression in the earliest stages of development may also operate in activated adult T lymphocytes.

scholarly journals Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release.

1984 ◽  
Vol 160 (6) ◽  
pp. 1717-1735 ◽  
Author(s):  
K Inaba ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Lymphocytes ◽  
B Cell ◽  
Interleukin 2 ◽  
Specific Antigen ◽  
Histocompatibility Complex ◽  
Ia Antigens ◽  
Antigen Presenting

Previous studies have shown that unprimed or resting T lymphocytes will grow and release lymphokines when stimulated by dendritic cells (DC). We now have examined the stimulatory requirements for antigen-primed or blast-transformed T cells. The latter were derived from dendritic/T cell clusters that developed during the primary mixed leukocyte reaction (MLR). The specificity of the blasts was established by a binding assay in which most T cells aggregated small B lymphocytes of the appropriate haplotype within 2 h at 4 or 37 degrees C. Since unprimed T cells did not aggregate allogeneic B cells, we suggest that DC induce T lymphocytes to express additional functioning receptors for antigen. Lyt-2-T blasts did not grow or release interleukin 2 or B cell helper factors unless rechallenged with specific alloantigen, whereupon growth (generation time of 14-18 h) and lymphokine release rapidly resumed. The blasts could be stimulated by allogeneic macrophages, B cells, and B lymphoblasts, whereas the primary MLR was initiated primarily by DC. responsiveness appeared restricted to the I region of the major histocompatibility complex, and varied directly with the level of Ia antigens on the stimulator cells. The interaction of B cells and T blasts was bidirectional. The T blasts would grow and form B cell helper factors, while the B cells grew and secreted antibody. However, the efficacy of T cell-mediated antibody formation was enhanced some 10-fold by the addition of specific antigen. Therefore, responses of resting helper T cells, then, are initiated by antigen plus DC. Once sensitized, T blasts interact independently with antigen presented by other leukocytes.

scholarly journals T cell development in normal and thymopentin-treated nude mice.

1982 ◽  
Vol 156 (4) ◽  
pp. 1057-1064 ◽  
Author(s):  
G E Ranges ◽  
G Goldstein ◽  
E A Boyse ◽  
M P Schield
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Population ◽  
Nude Mice ◽  
T Cell Development ◽  
T Cell Differentiation ◽  
Athymic Mice ◽  
Germ Free

The extent and diversity of T cell differentiation in nude athymic mice are matters of dispute. In this study, we examined the splenic T cell population of pathogen-free and germ-free nu/nu mice, treated or not treated with the pentapeptide analogue of thymopoietin (TP-5), in terms of TL, Qa-1, and Lyt phenotypes. At all ages, 50-60% of nu/nu splenocytes, enriched for T lymphocytes by removal of sIg+ cells, expressed T markers, as compared with greater than 85% in normal mice. At 2 mo of age, all nu/nu splenic T cells expressed the surface phenotype TL+:Thy-1+:Ly-123. This is abnormal in two respects: first, because expression of TL is normally confined to thymocytes; and second, because there was no evidence of the usual diversification into the subsets Ly-1 and Ly-23. From 10 wk of age onwards, diversification into Ly subsets was evident in nu/nu spleen, although the usual predominance of Ly-1 over Ly-123 cells was not attained, and some TL+ cells persisted. Also, the ratio of Qa-1+ to Qa-1- cells rose progressively to as high as 4:1 at 4-6 mo, in contrast to the usual ratio of approximately 1:1, regardless of age. In the spleens of nu/nu mice treated with TP-5 from 5-8 weeks of age and tested 1 wk later, the proportion of T cells was raised, though not to normal levels, the number of TL+ cells was reduced, and there was diversification into Ly sets.

Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice

2001 ◽  
Vol 281 (3) ◽  
pp. G764-G778 ◽  
Author(s):  
Andrew Burich ◽  
Robert Hershberg ◽  
Kim Waggie ◽  
Weiping Zeng ◽  
Thea Brabb ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bowel Disease ◽  
Wild Type ◽  
Immunodeficient Mice ◽  
Inflammatory Bowel ◽  
Rag 1

Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal immune response to luminal microbial antigens, with T lymphocytes mediating the colonic pathology. Infection with Helicobacter spp has been reported to cause IBD in immunodeficient mice, some of which lack T lymphocytes. To further understand the role of T cells and microbial antigens in triggering IBD, we infected interleukin (IL)-10−/−, recombinase-activating gene (Rag)1−/−, T-cell receptor (TCR)-α−/−, TCR-β−/−, and wild-type mice with Helicobacter hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype. IL-10−/−mice developed severe diffuse IBD with either H. bilis or H. hepaticus, whereas Rag1−/−, TCR-α−/−, TCR-β−/−, and wild-type mice showed different susceptibilities to Helicobacter spp infection. Proinflammatory cytokine mRNA expression was increased in the colons of Helicobacter-infected IL-10−/−and TCR-α−/−mice with IBD. These results confirm and extend the role of Helicobacter as a useful tool for investigating microbial-induced IBD and show the importance, but not strict dependence, of T cells in the development of bacterial-induced IBD.

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