Anti-CD28 mAb increase the induction of CD2 mediated apoptosis of lamina propria T lymphocytes in vivo

2000 ◽  
Vol 118 (4) ◽  
pp. A357
Author(s):  
Joerg C. Hoffmann ◽  
Karsten Peters ◽  
Sven Henschke ◽  
Martin Zeitz ◽  
Juergen Westermann
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria

scholarly journals Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes

2000 ◽  
Vol 192 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Bernd Sido ◽  
Jutta Braunstein ◽  
Raoul Breitkreutz ◽  
Christian Herfarth ◽  
Stefan C. Meuer
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria ◽  
Cell Cycle Progression ◽  
Redox Regulation ◽  
Cell Receptor ◽  
Proliferative Potential ◽  
Blood Monocytes ◽  
Intestinal Lamina Propria

Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor–ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.

Activation of isolated heterophils from chicks stimulated in vivo with salmonella enteritidis-immune lymphokines

1996 ◽  
Vol 54 ◽  
pp. 760-761
Author(s):  
R. B. Moyes ◽  
R. E. Droleskey ◽  
M. H. Kogut ◽  
J. R. DeLoach
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Salmonella Enteritidis ◽  
Intestinal Tract ◽  
Polymorphonuclear Cells ◽  
Subclinical Infection ◽  
Egg Products ◽  
Immune Lymphokines ◽  
Organ Invasion

Salmonella enteritidis (SE) is of great concern to the poultry industry due to the organism's ability to penetrate the intestinal mucosa of the laying hen and subsequently colonize the ovaries and yolk membrane. The resultant subclinical infection can lead to SE infection of raw eggs and egg products. Interference with the ability of the organism to invade has been linked to the activation and recruitment of inflammatory polymorphonuclear cells, heterophils, to the lamina propria of the intestinal tract.Recently it has been established that heterophil activation and increased resistance to SE organ invasion can be accomplished by the administration of SE-immune lymphokines (SE-ILK) obtained from supernatants of concanavalin-A stimulated SE immune T lymphocytes from SE hyperimmunized hens. Invasion of SE into the lamina propria provides a secondary signal for directing activated heterophils to the site of SE invasion.

Proteinase activated receptor (PAR)-2 protects against colitis in mice. Evidence for direct modulation of lamina propria T lymphocytes

2001 ◽  
Vol 120 (5) ◽  
pp. A135-A135
Author(s):  
S FIORUCCI ◽  
A MENCARELLI ◽  
B PALAZZETTI ◽  
E DISTRUTTI ◽  
J WALLACE ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria ◽  
Direct Modulation

scholarly journals Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dehua Lu ◽  
Yanpu Wang ◽  
Ting Zhang ◽  
Feng Wang ◽  
Kui Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Cytotoxic T Lymphocytes ◽  
Pet Imaging ◽  
Stage Migration ◽  
Cell Transfer ◽  
Tumor Infiltration ◽  
Antitumor Effects

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

scholarly journals Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Sanami ◽  
Fatemeh Azadegan-Dehkordi ◽  
Mahmoud Rafieian-Kopaei ◽  
Majid Salehi ◽  
Maryam Ghasemi-Dehnoo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Lymphocytes ◽  
Tertiary Structure ◽  
Therapeutic Vaccine ◽  
Epitope Prediction ◽  
Therapeutic Effects ◽  
Epitope Vaccine ◽  
In Vivo Experiments

AbstractCervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

scholarly journals O10: METFORMIN TREATMENT IMPROVES LYMPHOCYTE METABOLISM IN A MOUSE MODEL OF MAJOR SURGERY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
TF Jones ◽  
A Gutierrez ◽  
del Arroyo ◽  
SM Henson ◽  
GL Ackland
Keyword(s):  
T Lymphocytes ◽  
Mouse Model ◽  
T Lymphocyte ◽  
Major Surgery ◽  
P Value ◽  
Free Access ◽  
Mitochondrial Bioenergetics ◽  
Metformin Treatment ◽  
Respiratory Capacity

Abstract Introduction Lymphopaenia is common after major surgery and associated with poor outcome. T-lymphocytes restrain damaging innate inflammation. Major surgery impairs T-lymphocyte metabolism in humans, which promotes lymphopaenia. Metformin is known to improve mitochondrial bioenergetics in models of inflammation. Firstly, we hypothesised that a mouse model of major surgery would demonstrate impaired T-lymphocyte metabolism and secondly, that metformin treatment in vivo would reverse the phenotype. Method Male C57Bl/6 mice aged between 8 and 12 weeks were housed in a specific pathogen free environment with free access to food and water. Animals were dosed with either vehicle (phosphate buffered saline, 20 ml/kg) or metformin (250 mg/kg) daily via intraperitoneal injection for four days prior to and after surgery. A partial hepatectomy was performed under isofluorane anaesthesia. Naive littermates were used as controls. All experiments were performed according to the Animals (Scientific Procedures) Act 1986. Splenic T-lymphocytes were isolated by negative selection using magnetic beads. Mitochondrial bioenergetics were measured using a Seahorse Extracellular Flux analyser. Parametric statistical analysis was performed and a p-value < 0.05 was chosen to represent significance. Result T-lymphocytes demonstrated reduced spare respiratory capacity (SRC, 285 vs 497 %, p=0.004) after surgery compared to naive controls. Metformin treatment in vivo reversed this observation and SRC was comparable to naive (437 vs 497 %, p=0.34). Metformin treatment in vitro increased spare respiratory capacity in T-lymphocytes from mice after surgery compared to naive (change from untreated, 187 vs 91 %, p=0.03). Conclusion Perioperative metformin treatment improved T-lymphocyte metabolism in a mouse model of major surgery. Take-home message Metformin is a potential treatment for the lymphocyte metabolic dysfunction observed after surgery.

Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress

2005 ◽  
Vol 288 (3) ◽  
pp. R591-R599 ◽  
Author(s):  
Mitsuharu Okutsu ◽  
Kenji Ishii ◽  
Kai Jun Niu ◽  
Ryoichi Nagatomi
Keyword(s):  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Cxcr4 Expression ◽  
Peripheral Blood Mononuclear ◽  
Cycling Exercise ◽  
Ru 486 ◽  
Before And After ◽  
Stromal Cell Derived Factor ◽  
Chemokine Receptor 4

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1α/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.

11 beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon

1993 ◽  
Vol 264 (6) ◽  
pp. E951-E957 ◽  
Author(s):  
C. B. Whorwood ◽  
P. C. Barber ◽  
J. Gregory ◽  
M. C. Sheppard ◽  
P. M. Stewart
Keyword(s):  
Epithelial Cells ◽  
Lamina Propria ◽  
Hormone Receptors ◽  
Rat Kidney ◽  
Distal Colon ◽  
Hydroxysteroid Dehydrogenase ◽  
Neuroendocrine Cells ◽  
Rat Colon ◽  
Mrna Levels

In the rat kidney 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) maintains normal in vivo specificity for mineralocorticoid receptor (MR) by converting the active steroid corticosterone to inactive 11-dehydrocorticosterone, leaving aldosterone to occupy the MR. Clinical observations support the hypothesis that 11 beta-HSD also protects the distal colonic MR from glucocorticoid excess. We have measured 11 beta-HSD mRNA and activity along the rat colon and have analyzed the distribution of 11 beta-HSD, MR, and glucocorticoid receptor (GR) mRNA within rat distal colon using in situ hybridization. Levels of 11 beta-HSD mRNA (1.7 and 3.4 kb) and activity were higher in distal vs. proximal colon, paralleling reported MR mRNA levels. Within the distal colon mucosa both 11 beta-HSD immunoreactivity and mRNA was observed in cells in the lamina propria but not in epithelial cells. MR mRNA was present in surface epithelial cells, but was also colocalized with the same 11 beta-HSD-expressing cells in the lamina propria. In contrast GR mRNA was more uniformly distributed. The localization of MR mRNA to nonepithelial cells in the lamina propria, possibly neuroendocrine cells, suggests that mineralocorticoid-regulated sodium transport across colonic epithelial cells may also involve a paracrine mechanism. As with the kidney, exposure of active mineralocorticoid to the MR in these cells in the lamina propria is dictated by 11 beta-HSD in an autocrine fashion.

scholarly journals Identification of Two New HLA-A*1101-Restricted Tax Epitopes Recognized by Cytotoxic T Lymphocytes in an Adult T-Cell Leukemia Patient after Hematopoietic Stem Cell Transplantation

2005 ◽  
Vol 79 (15) ◽  
pp. 10088-10092 ◽  
Author(s):  
Nanae Harashima ◽  
Ryuji Tanosaki ◽  
Yukiko Shimizu ◽  
Kiyoshi Kurihara ◽  
Takao Masuda ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
T Lymphocytes ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cytotoxic T Lymphocytes ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Adult T Cell Leukemia

ABSTRACT We previously reported that Tax-specific CD8+ cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo.

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