Effects of Ca-Containing Phosphate Glasses on T Lymphocytes In Vitro

2005 ◽  
Vol 284-286 ◽  
pp. 597-602 ◽  
Author(s):  
A. Kesisoglou ◽  
Jonathan C. Knowles ◽  
I. Olsen
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Dna Synthesis ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Suppressor Cells ◽  
Phosphate Glasses ◽  
Activated T Cells

Calcium phosphate-based glasses (PG) are of interest as both scaffold and delivery materials for tissue rebuilding because of their chemical similarity to bone. Since it is essential that these materials exhibit local and systemic biocompatibility and do not adversely affect host tissues, the present study was undertaken to examine the effects of PG containing different amounts of Ca on human T lymphocytes in vitro. This was carried out by measuring the effects of extracts of the PG on the direct and mitogen-induced activation of T cells from human peripheral blood, as well as assessing CD4 and CD8, surface antigens which define T-helper and T-suppressor cells, respectively. The results showed that DNA synthesis by resting T lymphocytes was unaffected by all the PG. However, extracts of the PG containing 24 mol% of Ca caused a very marked inhibition of mitogen-induced T cell activation. This PG also reduced both the resting CD4+ and CD8+ T cells, as well as activated CD8+ cells. In contrast, high Ca-PG significantly augmented DNA synthesis by mitogen-activated T cells. These experiments show that PG containing differing levels of Ca can have pronounced and differential effects on the activation and function of T lymphocytes in vitro.

scholarly journals Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro.

1990 ◽  
Vol 110 (5) ◽  
pp. 1757-1766 ◽  
Author(s):  
W Risau ◽  
B Engelhardt ◽  
H Wekerle
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ifn Gamma

The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.

T cell-T cell activation in multiple sclerosis

1997 ◽  
Vol 3 (4) ◽  
pp. 238-242 ◽  
Author(s):  
JW Lindsey ◽  
RH Kerman ◽  
JS Wolinsky
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Viral Infections ◽  
Activated T Cells ◽  
In Vitro Proliferation

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

scholarly journals THYMUS-DERIVED CELL (T CELL) ACTIVATION BY HETEROLOGOUS ANTIGENS AS A REPLACEMENT OF SPECIFIC IMMUNE T CELLS IN THE TRANSFER OF THE SECONDARY RESPONSE TO SHEEP ERYTHROCYTES

1972 ◽  
Vol 136 (4) ◽  
pp. 715-721 ◽  
Author(s):  
J. J. Mond ◽  
T. Takahashi ◽  
G. J. Thorbecke
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Keyhole Limpet Hemocyanin ◽  
Secondary Response ◽  
Activated T Cells ◽  
Sheep Erythrocytes ◽  
Cell Responses ◽  
Heterologous Antigens

Spleen cells from LAF1 mice hyperimmune to sheep erythrocytes (SE) lost their ability to transfer a secondary response to irradiated recipients after incubation with anti-θ and rabbit complement in vitro. Small numbers of specific immune cells even when taken 3 days after a primary SE injection reconstituted the direct and indirect plaque-forming cell responses. Larger numbers of cells sensitized to B. abortus (or keyhole limpet hemocyanin), and given together with the corresponding antigen, also partially reconstituted the ability to respond to SE. This property was mediated by θ-bearing cells and was interpreted as due to a nonspecific humoral factor liberated by specifically activated T cells and acting on B cell proliferation or maturation.

Phenotypic and Functional Characterization Of a Novel Immature Hematopoietic Myeloid Suppressive Progenitor Cells Mobilized By G-CSF. Application To Gvhd Treatment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4476-4476
Author(s):  
Marie T Rubio ◽  
Maud D'Aveni ◽  
Tereza Coman ◽  
Julien Rossignol ◽  
Julie Bruneau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Acute Gvhd ◽  
Activated T Cells ◽  
Stem Cell Graft ◽  
Alloreactive T Cell

Background Myeloid derived suppressive cells (MDSCs) represent a heterogeneous population of cells endowed with immunosuppressive properties. They have been first described in the tumor microenvironment. Some mature MDSCs either induced by GM-CSF and IL-13 (Highfill et al., Blood 2010) or mobilized by G-CSF (Joo et al., Immunology 2009) have been reported to control experimental GVHD by inhibiting alloreactive T cell proliferation. We describe here the existence in mice and humans of a not yet characterized population of GCSF-mobilized hematopoïetic cells with phenotypic characteristics of immature MDSCs (called therefore pro-MDSCs) that can inhibit GVHD by a distinct mechanism than those described with classical mature MDSCs. Methods In the C57BL6 mouse and human, G-CSF mobilized MDSCs were collected and analyzed in the spleen and PBSC using several antibodies directed against various markers of maturity, lineage specific antigens and chemokine receptors. Depending on the expression of maturity antigens various population were sorted. In vitro, functions of sorted MDSC were analyzed by co-cultures with T cells activated either by anti-CD3 and CD28 mAbs or allogeneic dendritic cells. In vivo, the effect of various population of MDSCs on GVHD was assessed either by the transfer of murine C57BL6 (H-2b) cells (2x106 splenic T cells + 5x106 T depleted bone marrow cells +/- 0.5x106 MDSC subtypes) into lethally irradiated BALB/c (H-2d) recipients or by injecting 2x105 human pro-MDSCs with 2.5x106 human PBMC into 2 Gy irradiated Nod/SCID/gammac-/- mice. In 19 allografted patients, proportions of MDSC subpopulations contained in the peripheral stem cell graft were correlated to the occurrence of acute GVHD and to the post-transplant peripheral blood levels of conventional proliferating T cells and CD4+ CD25+ CD127low reguatory T cells (T regs). Results In the G-CSF mobilized cells, immature Lin- Sca1high cKithigh CD34+ CX3CR1+ CD16/32+ CD11b+ Ly6C+ and Lin- CD34+ HLA-DR- CD33high CD11blow CD14+ cell populations were identified in mice spleen and human PBSC, respectively. Because the pattern of maturity antigen expression, these populations were named pro-MDSCs. The mature MDSC counterparts shared the same differentiation phenotype without the markers of maturity. In vitro, both murine and human pro-MDSCs, but not the corresponding mature MDSCs, could inhibit the proliferation and induced the apoptosis of activated T cells (p<0,001). The inhibition of T cell activation by pro-MDSCs required IFN-gamma produced by activated T-cells and the production of NO by pro-MDSCs in response to IFN-gamma. NO suppressed T-cell functions through impaired responses to IL2 and induction of apoptosis. In vivo, in the C57BL6 to BALB/c GVHD model, the administration of murine pro-MDSCs significantly reduced the development of clinical and histological GVHD signs as compared to allografted mice without pro-MDSCs or with GCSF-mobilized mature MDSCs (p=0,03). Murine pro-MDSCs could migrate to site of allo-priming and induced the apoptosis of allogeneic T cells when compared to mice allografted without pro-MDSCs (p<0,01). In mice that had received pro-MDSCs, we observed that apoptotic T cells could be engulfed by phagocytes and that those phagocytes produced high levels of cytokines (IL-10, TGF-beta), which was associated with increased induced CD4+CD25+Foxp3+ T regs leading to the induction of tolerance. These observations were not seen in mice allografted without pro-MDSCs (p<0,05). Human pro-MDSCs could protect all xeno-grafted Nod/SCID/gamma c-/- mice from GVHD mortality as compared to 100% GVHD lethality in controlled xeno-grafted mice without pro-MDSCs (p<0,001). Allografted patients having received a stem cell graft containing levels of Pro-MDSCs >10% of the CD34+ fraction had a significantly reduced risk of developing grade II-IV acute GVHD (p= 0,04) and reduced numbers of proliferating conventional T cells but higher numbers of T regs in the peripheral blood on days 15 and 30 post-HSCT (p<0.05). No correlation between the occurrence of acute GVHD and the proportions of mature MDSCs contained in the graft was observed. Conclusion We have characterized a new homogeneous population of G-CSF mobilized immature MDSCs, which has been named pro-MDSC that can regulate alloreactive T cell activation in vitro and in vivo by inducing tolerance with potential therapeutic application in allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Upregulation of TRAIL expression on human T lymphocytes by interferon b and glatiramer acetate

2005 ◽  
Vol 11 (6) ◽  
pp. 652-657 ◽  
Author(s):  
N Arbour ◽  
E Rastikerdar ◽  
E McCrea ◽  
Y Lapierre ◽  
J Dörr ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Glatiramer Acetate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Therapeutic Effects ◽  
Activated T Cells ◽  
Trail Expression

We measured the in vivo and in vitro effects of interferon (IFN)b and glatiramer acetate (GA) on the expression of the regulatory molecule, tumor necrosis factor related apoptosis inducing ligand (TRAIL), in patients with multiple sclerosis (MS). We confirmed the prior observation that TRAIL is enhanced on anti-CD3 activated T cells by the in vitro addition of IFNβ. T cells from IFNβ-treated patients stimulated with anti-CD3 only, had higher levels of TRAIL than untreated patients, suggesting that in vivo IFNβ exposure has an effect on TRAIL expression in association with T cell activation. In vitro IFNβ-induced TRAIL upregulation on anti-CD3 or phytohemagglutinin-activated T cells was comparable for IFNβ-treated and non-treated MS patients and controls, indicating that IFN receptors were neither saturated nor down-regulated by current IFNβ therapy. Although GAin vivo orin vitro did not induce TRAIL, the IFNβ-GA combination in vitro enhanced TRAIL expression to higher levels than IFNβ alone on CD4+ T cells obtained from MS patients, regardless of GA treatment status, and healthy donors, and on GA reactive T cell lines derived from GA-treated patients or controls. Whether any observed therapeutic effects of GA/IFNβ combination therapy will correlate with TRAIL expression and function remains to be determined.

Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 606-615 ◽  
Author(s):  
Cristina Cerboni ◽  
Alessandra Zingoni ◽  
Marco Cippitelli ◽  
Mario Piccoli ◽  
Luigi Frati ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Protein A ◽  
T Cell Responses ◽  
Activated T Cells ◽  
Cell Responses

AbstractRecent evidence indicates that natural killer (NK) cells can negatively regulate T-cell responses, but the mechanisms behind this phenomenon as a consequence of NK–T-cell interactions are poorly understood. We studied the interaction between the NKG2D receptor and its ligands (NKG2DLs), and asked whether T cells expressed NKG2DLs in response to superantigen, alloantigen, or a specific antigenic peptide, and if this rendered them susceptible to NK lysis. As evaluated by FACS, the major histocompatibility complex (MHC) class I chain-related protein A (MICA) was the ligand expressed earlier on both CD4+ and CD8+ T cells in 90% of the donors tested, while UL16-binding protein-1 (ULBP)1, ULBP2, and ULBP3 were induced at later times in 55%–75% of the donors. By carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling, we observed that NKG2DLs were expressed mainly on T cells that had gone through at least one division. Real-time reverse-transcription polymerase chain reaction confirmed the expression of all NKG2DLs, except ULBP4. In addition, T-cell activation stimulated phosphorylation of ataxia-telangiectasia mutated (ATM), a kinase required for NKG2DLs expression after DNA damage, and ATM/Rad3-related kinase (ATR) inhibitors blocked MICA induction on T cells with a mechanism involving NF-κB. Finally, we demonstrated that activated T cells became susceptible to autologous NK lysis via NKG2D/NKG2DLs interaction and granule exocytosis, suggesting that NK lysis of T lymphocytes via NKG2D may be an additional mechanism to limit T-cell responses.

scholarly journals CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes.

1992 ◽  
Vol 175 (2) ◽  
pp. 353-360 ◽  
Author(s):  
M Azuma ◽  
M Cayabyab ◽  
D Buck ◽  
J H Phillips ◽  
L L Lanier
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Proliferative Response ◽  
Cell Activation ◽  
B Cell Activation ◽  
Rapid Responses ◽  
Cell Clones

Engagement of the CD3/T cell antigen receptor complex on small, resting T cells is insufficient to trigger cell-mediated cytotoxicity or to induce a proliferative response. In the present study, we have used genetic transfection to demonstrate that interaction of the B7-BB1 B cell activation antigen with the CD28 T cell differentiation antigen costimulates cell-mediated cytotoxicity and proliferation initiated by either anti-CD2 or anti-CD3 monoclonal antibody (mAb). Moreover, a B7-negative Burkitt's lymphoma cell line that fails to stimulate an allogeneic mixed lymphocyte response is rendered a potent stimulator after transfection with B7. The mixed leukocyte reaction proliferative response against the B7 transfectant is inhibited by either anti-CD28 or B7 mAb. We also demonstrate that freshly isolated small, resting human T cells can mediate anti-CD3 or anti-CD2 mAb-redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma transfected with human B7. These preexisting cytotoxic T lymphocytes in peripheral blood are present in both the CD4 and CD8 subsets, but are preferentially within the CD45RO+ "memory" population. While small, resting T cells apparently require costimulation by CD28/B7 interactions, this requirement is lost after T cell activation. Anti-CD3 initiates a cytotoxic response mediated by in vitro cultured T cell clones in the absence of B7 ligand. The existence of functional cytolytic T cells in the small, resting T cell population may be advantageous in facilitating rapid responses to immune challenge.

scholarly journals Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5381-5390 ◽  
Author(s):  
Pratima Sinha ◽  
Olesya Chornoguz ◽  
Virginia K. Clements ◽  
Konstantin A. Artemenko ◽  
Roman A. Zubarev ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Activated T Cells ◽  
Primary Tumors ◽  
Apoptosis Pathway

Abstract Myeloid-derived suppressor cells (MDSCs) inhibit adaptive and innate immunity and accumulate in the blood of persons with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turnover have not been identified. Mass spectrometry showed prominent expression of apoptosis pathway proteins, suggesting that MDSC turnover may be regulated by Fas-FasL–mediated apoptosis. This hypothesis was confirmed by showing that blood MDSCs induced by 3 mouse tumors were Fas+ and apoptosed in response to Fas agonist in vitro and to activated FasL+ T cells in vivo. FasL-deficient mice contained significantly more blood MDSCs than FasL+/+ mice, and after removal of primary tumors MDSCs regressed in STAT6−/− and CD1−/− mice but not in STAT6−/−FasL−/− or CD1−/−FasL−/− mice. Fas+ macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSCs. These results identify a new mechanism regulating MDSC levels in vivo and show a retaliatory relationship between T cells and MDSCs in that MDSCs suppress T-cell activation; however, once activated, T cells mediate MDSC apoptosis.

scholarly journals Voriconazole Inhibits Fungal Growth without Impairing Antigen Presentation or T-Cell Activation

2003 ◽  
Vol 47 (6) ◽  
pp. 1818-1823 ◽  
Author(s):  
Heather L. Van Epps ◽  
Marta Feldmesser ◽  
Eric G. Pamer
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Animal Models ◽  
T Cell Activation ◽  
Cell Activation ◽  
Fungal Growth ◽  
Antifungal Drugs ◽  
Isolation And Characterization

ABSTRACT Invasive aspergillosis (IA) is the most common life-threatening invasive mold infection worldwide. The principal therapy for IA is amphotericin B, despite its known toxicity and immunosuppressive side effects. Studies in animal models of IA suggest a role for T lymphocytes in the pathology of the disease, although the precise role for Aspergillus-specific T cells remains undefined. The isolation and characterization of T lymphocytes in animal models of IA are hampered by the rapid outgrowth of the fungus in cultures derived from infected organs. In the present study, we tested the abilities of the antifungal drugs caspofungin acetate and voriconazole to inhibit fungal growth in vitro as a means of maintaining cultures of T cells from Aspergillus-infected mice. We demonstrate that while both antifungal drugs are inhibitory, only voriconazole completely inhibited fungal growth, allowing long-term maintenance of T-cell cultures. In addition, voriconazole had no inhibitory effect on the activation and maturation of dendritic cells or the proliferation of T lymphocytes. Thus, voriconazole appears to be a promising agent for use in in vitro studies of Aspergillus-specific T lymphocytes in animal models of IA.

scholarly journals Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5247
Author(s):  
Frank Liang ◽  
Azar Rezapour ◽  
Louis Szeponik ◽  
Samuel Alsén ◽  
Yvonne Wettergren ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Functional Status ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Activated T Cells ◽  
Ifn Γ ◽  
Colorectal Cancer Patients

Although mouse models of CRC treatments have demonstrated robust immune activation, it remains unclear to what extent CRC patients’ APCs and TILs interact to fuel or quench treatment-induced immune responses. Our ex vivo characterization of tumor and adjacent colon cell suspensions suggest that contrasting environments in these tissues promoted inversed expression of T cell co-stimulatory CD80, and co-inhibitory programmed death (PD)-ligand1 (PD-L1) on intratumoral vs. colonic APCs. While putative tumor-specific CD103+CD39+CD8+ TILs expressed lower CD69 (early activation marker) and higher PD-1 (extended activation/exhaustion marker) than colonic counterparts, the latter had instead higher CD69 and lower PD-1 levels. Functional comparisons showed that intratumoral APCs were inferior to colonic APCs regarding protein uptake and upregulation of CD80 and PD-L1 after protein degradation. Our attempt to model CRC treatment-induced T cell activation in vitro showed less interferon (IFN)-γ production by TILs than colonic T cells. In this model, we also measured APCs’ CD80 and PD-L1 expression in response to activated co-residing T cells. These markers were comparable in the two tissues, despite higher IFN- γ exposure for colonic APCs. Thus, APCs within distinct intratumoral and colonic milieus showed different activation and functional status, but were similarly responsive to signals from induced T cell activation.

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