scholarly journals Dietary Supplementation with Transgenic Camelina sativa Oil Containing 20:5n-3 and 22:6n-3 or Fish Oil Induces Differential Changes in the Transcriptome of CD3+ T Lymphocytes

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3116
Author(s):  
Annette L. West ◽  
Elizabeth A. Miles ◽  
Lihua Han ◽  
Karen A. Lillycrop ◽  
Johnathan A. Napier ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Fish Oil ◽  
Seed Oil ◽  
Immune Cell ◽  
Camelina Sativa ◽  
Leukocyte Function ◽  
Before And After ◽  
Cell Transcriptome ◽  
Induced Changes

Eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) are important for leukocyte function. This study investigated whether consuming transgenic Camelina sativa (tCSO) seed oil containing both 20:5n-3 and 22:6n-3 is as effective as fish oil (FO) for increasing the 20:5n-3 and 22:6n-3 content of leukocytes and altering mitogen-induced changes to the T cell transcriptome. Healthy adults (n = 31) consumed 450 mg/day of 20:5n-3 plus 22:6n-3 from either FO or tCSO for 8 weeks. Blood was collected before and after the intervention. 20:5n-3 and 22:6n-3 incorporation from tCSO into immune cell total lipids was comparable to FO. The relative expression of the transcriptomes of mitogen-stimulated versus unstimulated T lymphocytes in a subgroup of 16 women/test oil showed 4390 transcripts were differentially expressed at Baseline (59% up-regulated), 4769 (57% up-regulated) after FO and 3443 (38% up-regulated) after tCSO supplementation. The 20 most altered transcripts after supplementation differed between test oils. The most altered pathways were associated with cell proliferation and immune function. In conclusion, 20:5n-3 and 22:6n-3 incorporation into immune cells from tCSO was comparable to FO and can modify mitogen-induced changes in the T cell transcriptome, contingent on the lipid matrix of the oil.

scholarly journals Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 667-671 ◽  
Author(s):  
F Lauria ◽  
D Raspadori ◽  
S Tura
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
B Cell ◽  
Proliferative Response ◽  
Lymphocytic Leukemia ◽  
Before And After ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.

Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4278-4284 ◽  
Author(s):  
Gerben Bouma ◽  
Siobhan Burns ◽  
Adrian J. Thrasher
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Immune Cell ◽  
Wild Type ◽  
Cytoskeletal Dynamics ◽  
T Cell Priming ◽  
And Migration ◽  
Priming Activity

The Wiskott-Aldrich syndrome (WAS) is characterized by defective cytoskeletal dynamics affecting multiple immune cell lineages, and leading to immunodeficiency and autoimmunity. The contribution of dendritic cell (DC) dysfunction to the immune dysregulation has not been defined, although both immature and mature WAS knockout (KO) DCs exhibit significant abnormalities of chemotaxis and migration. To exclude environmental confounders as a result of WAS protein (WASp) deficiency, we studied migration and priming activity of WAS KO DCs in vivo after adoptive transfer into wild-type recipient mice. Homing to draining lymph nodes was reduced and WAS KO DCs failed to localize efficiently in T-cell areas. Priming of both CD4+ and CD8+ T lymphocytes by WAS KO DCs preloaded with antigen was significantly decreased. At low doses of antigen, activation of preprimed wild-type CD4+ T lymphocytes by WAS KO DCs in vitro was also abrogated, suggesting that there is a threshold-dependent impairment even if successful DC–T cell colocalization is achieved. Our data indicate that intrinsic DC dysfunction due to WASp deficiency directly impairs the T-cell priming response in vivo, most likely as a result of inefficient migration, but also possibly influenced by suboptimal DC-mediated cognate interaction.

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.

scholarly journals In Vitro Expansion of T-Cell-Receptor Vα2.3+ CD4+ T Lymphocytes in HLA-DR17(3), DQ2+ Individuals upon Stimulation withMycobacterium tuberculosis

1999 ◽  
Vol 67 (8) ◽  
pp. 3800-3809 ◽  
Author(s):  
Semih Esin ◽  
Giovanna Batoni ◽  
Güher Saruhan-Direskeneli ◽  
Robert A. Harris ◽  
Johan Grunewald ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Soluble Extract ◽  
Repertoire Analysis ◽  
Before And After ◽  
Gene Usage

ABSTRACT The T-cell receptor (TCR) Vα/β gene product expression upon in vitro stimulation with mycobacteria was investigated to assess whether T-cell proliferation was associated with any specific TCR V gene usage. T-cell-enriched populations from peripheral blood ofMycobacterium bovis BCG-vaccinated healthy blood donors were stimulated in vitro with live or killed M. tuberculosis or with a soluble extract thereof. TCR Vα/β repertoire analysis of reactive CD4+ and CD8+ T cells revealed a selective HLA-DR17(3), DQ2-restricted expansion of Vα2.3+ CD4+ T cells upon stimulation with live M. tuberculosis or its soluble extract. Third-complementarity-determining-region (CDR3) length analysis of the expanded Vα2.3+ T cells indicated an oligoclonal pattern with short CDR3 lengths in six of seven HLA-DR17(3), DQ2+individuals tested. In addition, Vα/Vβ repertoire analysis of T lymphocytes from a DR17(3), DQ2+ donor before and after BCG vaccination revealed that positivity of skin test reactivity was associated with expansion of Vα2.3+ CD4+ T lymphocytes with preferential use of a short CDR3 peak length after in vitro stimulation. Separation of M. tuberculosis soluble extract by fast protein liquid chromatography (FPLC) purification indicated that fractions corresponding to molecular masses of 60 to 70 and 15 to 25 kDa were particularly effective in eliciting Vα2.3+ CD4+ T-cell expansion.

scholarly journals ID:4007 Immune-cell base for cancer therapy

2017 ◽  
Vol 4 (S) ◽  
pp. 10
Author(s):  
Van Thanh Ta ◽  
Thinh Huy Tran ◽  
Binh Thanh Nguyen ◽  
Linh Quy Nguyen ◽  
Hoai Quy Nguyen ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Immune Cell ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Adoptive T Cell Therapy ◽  
Target Cells ◽  
T Cell Therapy ◽  
Mhc Molecules

The development of immune cell-based approaches for treatment of cancer has been actively investigated for many years. One strategy that has been demonstrated as an effective method for cancer treatment is adoptive T cell therapy. The principle of this method is using Cytotoxic T lymphocytes (CTL), a crucial component of the adaptive immune system that aids in the control of intracellular pathogens. Effector CTL have the capacity to promote the apoptotic death of specifically targeted cells, using a combination of granule (perforin/granzyme)-and receptor (Fas/tumor necrosis factor)-mediated mechanisms. CTL recognize specific antigen on target cells using an unique T-cell receptor (TCR) when they are presented by class I major histocompatibility (MHC) molecules. In this study, we demonstrated that T lymphocytes were activated and dramatically expanded by stimulation with anti-CD3/CD28 antibodies and culture in the present of IL-2, IL-15 and IL-21 cytokines. These T cells exhibited a predominantly activated phenotype as manifested by an increase in the percentage of cells expressing CD8 and generation of various cytokines such as IL-2, INFγ and TNFa. These findings indicate that stimulation by anti- CD3/CD28 generated effector CTL in adoptive T-cell therapy for cancer.

scholarly journals Colchicine interferes with L-selectin and leukocyte function-associated antigen-1 expression on human T lymphocytes and inhibits T cell activation.

1996 ◽  
Vol 7 (4) ◽  
pp. 594-601
Author(s):  
N Perico ◽  
D Ostermann ◽  
M Bontempeill ◽  
M Morigi ◽  
C S Amuchastegui ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Surface Expression ◽  
Microtubule Assembly ◽  
Leukocyte Function ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Colchicine, which inhibits cell microtubule assembly by preventing polymerization of tubulin monomers, inhibits cell-mediated immune responses and promotes long-term survival of major histocompatibility complex-incompatible renal allografts in rats. Here we evaluated the effect of blocking cell microtubule assembly by colchicine on T cell and endothelial cell adhesion receptors involved in transducing signals for T cell activation. By using immunofluorescence flow cytometry analysis, evidence is presented that colchicine, in a dose-dependent fashion, downregulated L-selectin and leukocyte function-associated antigen-1, but not CD2 and CD44 on the surface of naive human peripheral blood lymphocytes. This effect was confirmed in two subsets of T lymphocytes, namely, CD45RA- and CD45RO-positive cells. However, colchicine did not influence the rapid shedding of L-selectin from T lymphocytes exposed to activating stimuli. Colchicine inhibited expression of interleukin-2 receptor on activated T lymphocytes. This effect was observed when T lymphocytes were stimulated with both anti-CD3 and anti L-selectin monoclonal antibodies. Colchicine also inhibited lymphocyte function in vitro as documented by inhibition of the human mixed lymphocyte response in a dose-dependent fashion. Moreover, colchicine downregulated surface expression of intercellular adhesion molecule-1 and E-selectin on activated human umbilical vein endothelial cells. These results indicate that blocking cell microfubule assembly inhibits surface expression of adhesion molecules on T cells and endothelial cells, and provides insights into the complex mechanisms of the action of colchicine in vivo.

scholarly journals Dietary supplementation with seed oil from transgenic Camelina sativa induces similar increments in plasma and erythrocyte DHA and EPA to fish oil in healthy humans

2020 ◽  
Vol 124 (9) ◽  
pp. 922-930 ◽  
Author(s):  
Annette L. West ◽  
Elizabeth A. Miles ◽  
Karen A. Lillycrop ◽  
Lihua Han ◽  
Johnathan A. Napier ◽  
...  
Keyword(s):  
Fish Oil ◽  
Seed Oil ◽  
Cell Function ◽  
Venous Blood ◽  
Dietary Supplementation ◽  
Camelina Sativa ◽  
Human Consumption ◽  
Healthy Humans ◽  
Epa And Dha ◽  
Significant Difference

AbstractEPA and DHA are required for normal cell function and can also induce health benefits. Oily fish are the main source of EPA and DHA for human consumption. However, food choices and concerns about the sustainability of marine fish stocks limit the effectiveness of dietary recommendations for EPA + DHA intakes. Seed oils from transgenic plants that contain EPA + DHA are a potential alternative source of EPA and DHA. The present study investigated whether dietary supplementation with transgenic Camelina sativa seed oil (CSO) that contained EPA and DHA was as effective as fish oil (FO) in increasing EPA and DHA concentrations when consumed as a dietary supplement in a blinded crossover study. Healthy men and women (n 31; age 53 (range 20–74) years) were randomised to consume 450 mg/d EPA + DHA provided either as either CSO or FO for 8 weeks, followed by 6 weeks washout and then switched to consuming the other test oil. Fasting venous blood samples were collected at the start and end of each supplementation period. Consuming the test oils significantly (P < 0·05) increased EPA and DHA concentrations in plasma TAG, phosphatidylcholine and cholesteryl esters. There were no significant differences between test oils in the increments of EPA and DHA. There was no significant difference between test oils in the increase in the proportion of erythrocyte EPA + DHA (CSO, 12 %; P < 0·0001 and FO, 8 %; P = 0·02). Together, these findings show that consuming CSO is as effective as FO for increasing EPA and DHA concentrations in humans.

scholarly journals Single-cell transcriptome analysis of the immunosuppressive effect of differential expression of tumor PD-L1 on responding TCR-T cells

2020 ◽  
Author(s):  
Renpeng Ding ◽  
Shang Liu ◽  
Shanshan Wang ◽  
Huanyi Chen ◽  
Fei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Clusters ◽  
Cellular Assays ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractPD-L1 expression levels in tumors do not consistently predict cancer patients’ response to PD-(L)1 inhibitors. We therefore evaluated how tumor PD-L1 levels affect the anti-PD-(L)1 efficacy and T cell function. We used MART-1-specific TCR-T cells (TCR-TMART-1) stimulated with MART-127-35 peptide-loaded MEL-526 tumor cells with different proportions of them expressing PD-L1 to perform cellular assays and high-throughput single-cell RNA sequencing. Compared to control T cells, TCR-TMART-1 were more sensitive to exhaustion and secreted lower pro-inflammatory but higher anti-inflammatory cytokines with increasing proportions of PD-L1+ tumor cells. The colocalization of T cells and tumor cells in gene clusters correlated negatively with the proportion of PD-L1+ tumor cells and positively with immune cell cytotoxicity. Moreover, elevated proportion of PD-L1+ tumor cells increased PD-L1 expression and decreased PD-1 expression on T cells and enhanced T cell death. The expression of PD-1 and PD-L1 in T cells and macrophages also correlated positively with COVID-19 severity.

scholarly journals Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 667-671
Author(s):  
F Lauria ◽  
D Raspadori ◽  
S Tura
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
B Cell ◽  
Proliferative Response ◽  
Lymphocytic Leukemia ◽  
Before And After ◽  
Cell Chronic Lymphocytic Leukemia

Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.

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