scholarly journals Mildly oxidized low-density lipoproteins suppress the proliferation of activated CD4+ T-lymphocytes and their interleukin 2 receptor expression in vitro

1998 ◽  
Vol 330 (2) ◽  
pp. 659-666 ◽  
Author(s):  
Sylvie CASPAR-BAUGUIL ◽  
Majed SAADAWI ◽  
Anne NEGRE-SALVAYRE ◽  
Mogens THOMSEN ◽  
Robert SALVAYRE ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Clone ◽  
Peripheral Blood Lymphocytes ◽  
Cd4 T Cell ◽  
Activated T Cells ◽  
T Cell Clone ◽  
Activated T Lymphocytes

Activated T-lymphocytes are present in early atherosclerotic lesions where they may interact with oxidized low-density lipoproteins (oxLDLs). In this study the non-specific effect of oxLDLs on the activation of T-cells in vitro was investigated. LDLs were oxidized by UV irradiation and characterized by a low level of lipid peroxidation and only slight apolipoprotein B modification. Peripheral blood lymphocytes from normal individuals were stimulated in vitro with the polyclonal activator phytohaemagglutinin in the presence of various doses of LDLs and oxLDLs. LDLs enhanced the proliferation of peripheral blood lymphocytes at doses up to 100 μg/ml but were inhibitory at 200 μg/ml, whereas low doses of oxLDLs (over 10 μg/ml) inhibited the proliferation. OxLDLs also inhibited the proliferative responses of an alloreactive CD4+ T-cell line immortalized by Herpes virus saimiri and an influenza haemagglutinin-specific CD4+ T-cell clone. Viability tests using Trypan Blue exclusion or expression of Apo2.7, an apoptosis marker, did not indicate any significant cell death at doses up to 100 μg/ml oxLDL. At this concentration, cell-cycle analysis showed an accumulation of cells at the G1/S interface in the CD4+ cell clone, without significant DNA fragmentation. The expression of the activation antigen CD25 on T-lymphocytes (on phytohaemagglutinin-activated T-cells and on CD4+ T-cell clone), requisite to the commitment of activated T-cells from G1 phase to S phase, was also inhibited by oxLDLs whereas expression of other activation antigens such as CD69 and HLA-DR was unchanged. In conclusion, these data show that mildly oxidized LDLs inhibit the proliferation and CD25 expression of activated T-lymphocytes and suggest that oxLDLs may slow down the T-cell response in atherosclerotic lesions.

Cytotoxicity Is Not Required for the Anti-Leukemia Efficacy of Human H-Y-Specific CD4+ T Lymphocytes In Vivo.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3553-3553
Author(s):  
Attilio Bondanza ◽  
Lothar Hambach ◽  
Zohara Aghai ◽  
Monica Casucci ◽  
Bart Nijmeijer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Clone ◽  
Scid Mice ◽  
Helper T Cell ◽  
T Cell Clone ◽  
Control Clone

Abstract Abstract 3553 Poster Board III-490 Introduction Minor histocompatibility antigens (mHag) play a major role in the graft-versus-leukemia (GvL) effect following HLA-matched allogeneic hemopoietic cell transplantation (allo-HCT). Clinically, the GvL effect coincides with the emergence of mHag-specific CD8+ cytotoxic T lymphocytes (CTL). Experimentally, targeting a single mHag with human CD8+ CTL has a major anti-leukemia effect in NOD/scid mice. Altogether, these observations suggest that mHag-specific cytotoxicity by CD8+ T cells is an important component of the GvL effect. In contrast, little is known on the contribution of mHag-specific CD4+ T cells. Female-to-male allo-HCT is characterized by a low rate of leukemia relapse, indicating that H-Y-encoded mHag are potent leukemia-regression antigens. Earlier, we described a DRB3*0301-restricted H-Y mHag epitope inducing CD4+ helper T-cell responses in H-Y-mismatched HLA-matched allo-HCT. Aim: The aim of this study is to elucidate the role of mHag-specific human CD4+ T lymphocytes on the GvL effect. Methods The ALL-CM leukemia cell line, derived from a male (i.e. H-Y+) HLA-A0201+, DRB30301+ patient, reproducibly engrafts in NOD/scid mice after administration of 10×106 cells. Both an HLA-A0201-restricted H-Y-specific CD8+ CTL clone and the DRB30301-restricted H-Y-specific CD4+ helper T-cell clone that we earlier described were used to investigate the anti-leukemia efficacy of CD8+ and CD4+ T cells in NOD/scid mice. Results In vitro, the CD8+ H-Y specific CTL clone was highly cytotoxic against the ALL-CM leukemia. The H-Y specific CD4+ helper T-cell clone did not lyse the leukemia, but produced IFN-γ upon recognition. Infusion of the H-Y-specific CD8+ CTL clone (25×106 cells/mouse) 3 days after ALL-CM leukemia challenge significantly delayed leukemia progression by 3 weeks compared to a CMV-specific CD8+ CTL control clone (p<0,001). Despite no measurable in vitro cytotoxicity, the H-Y-specific CD4+ helper T-cell clone (25×106 cells/mouse) delayed leukemia progression by 2 weeks compared to a leukemia non-reactive HLA-DR1-specific CD4+ helper T-cell control clone (p<0,001). In vitro co-incubation of the H-Y-specific CD4+ helper T-cell clone did not influence leukemia proliferation but induced up-regulation of MHC-class I and II, CD80, CD86 and CD40. In vitro, pre-incubation of leukemia cells with the H-Y-specific CD4+ helper T-cell clone irradiated did not improve the in vivo anti-leukemia efficacy of the H-Y-specific CD8+ CTL clone. Co-infusion of the H-Y specific CD4+ helper T-cell clone did not augment the in vivo persistence of the H-Y-specific CD8+ CTL T-cell clone. Nevertheless, the co-infusion resulted in a delay in leukemia progression of approximately 5 weeks, suggesting an additive, non overlapping anti-leukemia mechanism. Conclusions Minor Hag-specific human CD4+ T lymphocytes may contribute to the GvL effect through a direct, non cytotoxic mechanism, which could be additive to that of CD8+ CTL. The nature of this non cytotoxic GvL effect is currently under investigation. A.B. and L.H. equally contributed to this study. Disclosures: No relevant conflicts of interest to declare.

TIRC7 and HLA-DR axis contributes to inflammation in multiple sclerosis

2014 ◽  
Vol 20 (9) ◽  
pp. 1171-1181 ◽  
Author(s):  
JM Frischer ◽  
M Reindl ◽  
B Künz ◽  
T Berger ◽  
S Schmidt ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Ex Vivo ◽  
Peripheral Blood Lymphocytes ◽  
Cytokine Expression ◽  
Hla Dr ◽  
T Cell Clone

Background and objective: Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS). Methods: Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model. Results: TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7+ T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone. Conclusion: Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.

scholarly journals TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Trudy Straetemans ◽  
Mandy van Brakel ◽  
Sabine van Steenbergen ◽  
Marieke Broertjes ◽  
Joost Drexhage ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
Cell Clone ◽  
Cd4 T Cell ◽  
Adoptive Therapy ◽  
Effective Response ◽  
Cell Functions ◽  
T Cell Clone

Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly characterized TCRαβgenes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRsin vitroupon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.

scholarly journals Cytotoxic T cells both produce and respond to interleukin 2

1984 ◽  
Vol 159 (2) ◽  
pp. 647-652 ◽  
Author(s):  
L Andrus ◽  
A Granelli-Piperno ◽  
E Reich
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
In Vitro Response

Interleukin 2 (IL-2) is a T cell-derived lymphokine that serves as a cofactor for the in vitro response of T lymphocytes to antigen and plays an important role in regulating the growth and/or differentiation of these cells (1, 2). It has been postulated (2, 3) that IL-2 is produced by a discrete regulatory T cell subset, with its effects being exerted on a second, functionally distinct subpopulation of T cells. Cytotoxic T cells have been included in the IL-2-responsive subset (3). Several models of immune regulation have further assumed that the T lymphocyte pool is divided into a complex array of genetically preprogrammed T cell subtypes, each performing a specific regulatory or effector function (4, 5). However, recent results from several laboratories (6-8) have failed to support such a strict functional subdivision of the T cell pool. The availability of highly purified mouse IL-2 (1) prompted us to reevaluate the distinction, if any, between IL-2-producing and IL-2- responsive T cells. For this purpose, we resorted to a cell-cloning procedure using activated T lymphocytes that were maintained only for short periods in culture. T cell clones were tested for cytotoxic activity, responsiveness to IL-2, and for the capacity to produce IL-2 after appropriate stimulation. We found no evidence for the existence of a major functional subdivision involving these parameters among alloantigen-activated T cells: the majority of clones analyzed could perform all three functions.

scholarly journals IL4I1 Accelerates the Expansion of Effector CD8+ T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Marie-Line Puiffe ◽  
Aurélie Dupont ◽  
Nouhoum Sako ◽  
Jérôme Gatineau ◽  
José L. Cohen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Clone

IL4I1 is an immunoregulatory enzyme that inhibits CD8 T-cell proliferation in vitro and in the tumoral context. Here, we dissected the effect of IL4I1 on CD8 T-cell priming by studying the differentiation of a transgenic CD8 T-cell clone and the endogenous repertoire in a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. Unexpectedly, we show that IL4I1 accelerates the expansion of functional effector CD8 T cells during the first several days after infection and increases the average affinity of the elicited repertoire, supporting more efficient LCMV clearance in WT mice than IL4I1-deficient mice. Conversely, IL4I1 restrains the differentiation of CD8 T-cells into long-lived memory precursors and favors the memory response to the most immunodominant peptides. IL4I1 expression does not affect the phenotype or antigen-presenting functions of dendritic cells (DCs), but directly reduces the stability of T-DC immune synapses in vitro, thus dampening T-cell activation. Overall, our results support a model in which IL4I1 increases the threshold of T-cell activation, indirectly promoting the priming of high-affinity clones while limiting memory T-cell differentiation.

scholarly journals SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Chen ◽  
Xianying Fang ◽  
Yuan Gao ◽  
Ke Shi ◽  
Lijun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Contact Hypersensitivity ◽  
Immunosuppressive Activity ◽  
Con A ◽  
Activated T Cells ◽  
Picryl Chloride

Abstract Background T lymphocytes play an important role in contact hypersensitivity. This study aims to explore the immunosuppressive activity of SBF-1, an analog of saponin OSW-1, against T lymphocytes in vitro and in vivo. Methods Proliferation of T lymphocytes from lymph nodes of mice was determined by MTT assay. Flow cytometry analysis was performed to assess T cell activation and apoptosis. Levels of cytokines were determined by PCR and ELISA. BALB/c mice were sensitized and challenged with picryl chloride and thickness of left and right ears were measured. Results SBF-1 effectively inhibited T lymphocytes proliferation induced by concanavalin A (Con A) or anti-CD3 plus anti-CD28 at a very low dose (10 nM) but exhibited little toxicity in non-activated T lymphocytes at concentrations up to 10 μM. In addition, SBF-1 inhibited the expression of CD25 and CD69, as well as he phosphorylation of AKT in Con A-activated T cells. SBF-1 also induced apoptosis of activated T cells. In addition, SBF-1 also downregulated the induction of the T cell cytokines, IL-2 and IFN-γ in a dose-dependent manner. Furthermore, SBF-1 significantly suppressed ear swelling and inflammation in a mouse model of picryl chloride-induced contact hypersensitivity. Conclusions Our findings suggest that SBF-1 has an unique immunosuppressive activity both in vitro and in vivo mainly through inhibiting T cell proliferation and activation. Its mechanism appears to be related to the blockage of AKT signaling pathway.

scholarly journals BINDING OF AGGREGATED γ-GLOBULIN TO ACTIVATED T LYMPHOCYTES IN THE GUINEA PIG

1974 ◽  
Vol 139 (4) ◽  
pp. 1002-1012 ◽  
Author(s):  
John A. van Boxel ◽  
David L. Rosenstreich
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Lymphocytes ◽  
Guinea Pig ◽  
Surface Membrane ◽  
Cell Populations ◽  
Cell Marker ◽  
Activated T Cells ◽  
Activated T Lymphocytes

Heat-aggregated guinea pig γ-globulin was shown to bind to the surface membrane of a subclass of guinea pig T lymphocytes. Cells of this subpopulation were identified as T lymphocytes because these cells did not stain for surface Ig (a B-cell marker) but did form spontaneous E-rosettes with rabbit erythrocytes (a T-cell marker). A strikingly high proportion of such aggregate-binding (Agg+), E-rosette-forming (E-rosette+), but surface Ig-negative (Ig-) cells were found in an inflammatory exudate. Thus purified peritoneal exudate lymphocytes (PELs) are known to consist of over 90% T cells, and 59% of these cells bound aggregates. 10% of these Agg+ Ig- E-rosette+ cells were found in draining lymph node cell populations and none in thymus cell populations. The high frequency amongst PELs suggested that these Aggregate+ Ig- E-rosette+ cells might be activated T cells as these are known to occur in high proportion in PEL populations. Confirmatory evidence for this postulate was provided by the striking increase (from 10% to 46%) of Ig- E-rosette+ cells that bound aggregates when lymph node cells were activated by antigen stimulation in vitro.

scholarly journals Demonstration of functional CD40 in B-lineage acute lymphoblastic leukemia cells in response to T-cell CD40 ligand

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5162-5170 ◽  
Author(s):  
N Renard ◽  
M Lafage-Pochitaloff ◽  
I Durand ◽  
V Duvert ◽  
L Coignet ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Clone ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Activated T Cells ◽  
T Cell Clone ◽  
B Lineage

Because activated T cells were previously shown to induce proliferation of human normal B-cell precursors (BCP) via the CD40 pathway, we investigated the effects of T cells on leukemic blasts isolated from patients with B-lineage acute lymphoblastic leukemia (BCP-ALL). An anti- CD3 activated human CD4+ T-cell clone was found to induce significant call proliferation in four of nine BCP-ALL samples analyzed. In one of these cases, the T-cell effect was clearly dependent on interaction between CD40 and its ligand. Accordingly, a more thorough analysis was performed on this particular leukemia (case 461, adult early pre-B-ALL, mBCR+, Philadelphia+, i(9q)+). Thus, autologous CD4+ T cells isolated from the patient were also able to induce CD40-dependent proliferation of the leukemic blasts. Analysis of the phenotype after coculture showed that, among the CD19+ cells, a proportion gradually lost expression of CD10 and CD34, whereas some cells acquired CD23. In addition, and in contrast with normal BCP, activated T cells promoted maturation of a subset of the case 461 leukemic cells into surface IgM+ cells. The leukemic origin of the cycling and the maturing cells was assessed by the presence of i(9q), a chromosomal abnormality associated with this leukemia and evidenced by fluorescence in situ hybridization. Taken together, these results show that leukemic BCP can be activated via CD40 but that not all cases display detectable stimulation in response to T cells despite their expression of CD40. In addition, the present data suggest that CD4+ T cells could potentially play a role in the physiology of BCP-ALL.

scholarly journals CD4+ cytolytic T cell clone confers protection against murine malaria.

1990 ◽  
Vol 172 (5) ◽  
pp. 1353-1357 ◽  
Author(s):  
M Tsuji ◽  
P Romero ◽  
R S Nussenzweig ◽  
F Zavala
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Passive Transfer ◽  
Cd4 T Cell ◽  
Spleen Cells ◽  
Ifn Gamma ◽  
Degree Of Protection ◽  
T Cell Clone ◽  
High Degree

A CD4+ T cell clone (A1.6) was derived from spleen cells of mice immunized with irradiated sporozoites. This T cell clone recognizes an antigen that is shared by sporozoites and blood forms of Plasmodium berghei and differs from the circumsporozoite protein. Clone A1.6 displays cytotoxic activity, produces IFN-gamma and IL-2 in vitro, and recognizes the plasmodial antigen in the context of the class II I-Ed molecule. Passive transfer of this CD4+ clone into naive mice resulted in a high degree of protection against sporozoite challenge.

scholarly journals The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages.

1991 ◽  
Vol 174 (3) ◽  
pp. 499-505 ◽  
Author(s):  
L E Smith ◽  
M Rodrigues ◽  
D G Russell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Clone ◽  
Vitro Model ◽  
Leishmania Parasites

Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H-2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti-IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event.

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