scholarly journals The Fc receptor on thymus-derived lymphocytes. IV. Inhibition of binding of antigen-antibody complexes to Fc receptor-positive T cells by anti-Ia sera.

1977 ◽  
Vol 145 (1) ◽  
pp. 187-203 ◽  
Author(s):  
R D Stout ◽  
D B Murphy ◽  
H O McDevitt ◽  
L A Herzenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Fc Receptor ◽  
Inhibition Assay ◽  
Functional Heterogeneity ◽  
Peripheral T Cells ◽  
Binding Inhibition ◽  
Antigen Antibody ◽  
Binding Inhibition Assay

Treatment of splenic T lymphocytes with anti-Ia antiserum inhibits the binding of antigen-antibody (AgAb) complexes to the majority (less than 50%) of Fc receptor-positive (FcR+) T cells. A similar inhibition was observed with anti-H-2D and anti-H-2K sera but not with anti-Thy 1.2. Despite the presence of Ia determinants on peripheral T cells, as established by the inhibition of AgAb binding, Ia could not be detected on peripheral T cells by immunofluorescence assays. Data obtained with the AgAb-binding inhibition assay indicate that determinants controlled by loci mapping in the I-A and I-C, S, or G regions are present on the FcR+ T cells. Evidence is presented that subpopulations of T cells within the FcR+ T-cell population may be distinguishable on the basis of which I-region-controlled determinant is expressed. The data are discussed in terms of phenotypic and functional heterogeneity of T lymphocytes.

scholarly journals Post-thymic T lymphocyte maturation during ontogenesis.

1981 ◽  
Vol 154 (3) ◽  
pp. 581-593 ◽  
Author(s):  
P F Piguet ◽  
C Irle ◽  
E Kollatte ◽  
P Vassalli
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Lectin Binding ◽  
T Cell Subsets ◽  
Proliferating Cells ◽  
Peanut Lectin ◽  
Peripheral T Cells

Peripheral T lymphocytes from newborn (4-6-d-old) mice, isolated from the spleen or lymph nodes, show phenotypic features of immature cortical thymocytes, such as high frequencies of proliferating cells and of peanut lectin-binding cells. These are features of peripheral T cells of recent thymic origin, as shown by in situ labeling of thymocytes and subsequent observation of the migrants to the spleen, which were mainly peanut lectin-binding cells. The function of newborn peripheral T cells was compared, on a per T cell basis, with that of thymocytes and of fully mature peripheral T cells of the adult, using preparations of newborn lymph node cells containing approximately 80% of T lymphocytes. They were strikingly (about 10-fold) less competent than adult T cells in their phytohemagglutinin responsiveness, their capacities to induce a graft vs. host reaction, to proliferate in the mixed lymphocyte reaction, and to help B lymphocytes in a humoral response in vivo and in vitro. In contrast, newborn T lymphocytes were comparable to those of adults in their capacity to generate cytotoxic T lymphocytes. No suppressive effect of newborn T lymphocytes could be demonstrated in several of these assays. These results argue for an asynchronous maturation of two T cell subsets during ontogeny and demonstrate that at least some T lymphocytes leave the thymus as immature T cells resembling cortical thymocytes and further mature at the periphery. Investigation of mice submitted to thymectomy of 5 d of age showed that these incompetent post-thymic T lymphocytes are capable of considerable expansion and maturation in the peripheral lymphoid organs in the absence of a thymic influence.

Human T-cell lymphotropic virus oncoprotein Tax represses TGF-β1 signaling in human T cells via c-Jun activation: a potential mechanism of HTLV-I leukemogenesis

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4129-4138 ◽  
Author(s):  
Bertrand Arnulf ◽  
Aude Villemain ◽  
Christophe Nicot ◽  
Elodie Mordelet ◽  
Pierre Charneau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dna Binding ◽  
Binding Activity ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Dna Binding Activity ◽  
Human T Cell ◽  
Peripheral T Cells ◽  
Tgf Β1

Human T-cell leukemia virus I is the etiologic agent of adult T-cell leukemia (ATL), an aggressive T-cell malignancy. The viral oncoprotein Tax, through the activation of nuclear factorκB (NF-κB), CCAAT-enhancer binding protein (CREB), and activated protein-1 (AP-1) pathways, is a transcriptional regulator of critical genes for T-cell homeostasis. In ATL cells, activated AP-1 complexes induce the production of transforming growth factor β1 (TGF-β1). TGF-β1 is an inhibitor of T-cell proliferation and cytotoxicity. Here we show that, in contrast to normal peripheral T cells, ATL cells are resistant to TGF-β1–induced growth inhibition. The retroviral transduction of the Tax protein in peripheral T cells resulted in the loss of TGF-β1 sensitivity. Transient transfection of Tax in HepG2 cells specifically inhibited Smad/TGF-β1 signaling in a dose-dependent manner. In the presence of Tax transfection, increasing amounts of Smad3 restored TGF-β1 signaling. Tax mutants unable to activate NF-κB or CREB pathways were also able to repress Smad3 transcriptional activity. Next we have demonstrated that Tax inhibits TGF-β1 signaling by reducing the Smad3 DNA binding activity. However, Tax did not decrease the expression and the nuclear translocation of Smad3 nor did it interact physically with Smad3. Rather, Tax induced c-Jun N-terminal kinase (JNK) activity and c-Jun phosphorylation, leading to the formation of Smad3/c-Jun complexes. Whereas c-Jun alone abrogates Smad3 DNA binding, cotransfection of Tax and of a dominant-negative form of JNK or a c-Jun antisense-restored Smad3 DNA binding activity and TGF-β1 responsiveness. In ATL and in normal T cells transduced by Tax, c-Jun was constitutively phosphorylated. Thus, we describe a new function of Tax, as a repressor of TGF-β1 signaling through JNK/c-Jun constitutive activation, which may play a critical role in ATL leukemogenesis.

scholarly journals Quantitative assessment of the pool size and subset distribution of cytolytic T lymphocytes within human resting or alloactivated peripheral blood T cell populations.

1983 ◽  
Vol 158 (2) ◽  
pp. 571-585 ◽  
Author(s):  
A Moretta ◽  
G Pantaleo ◽  
L Moretta ◽  
M C Mingari ◽  
J C Cerottini
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Great Majority ◽  
T Cell Subsets ◽  
Cytolytic T Lymphocytes ◽  
Subset Distribution

In order to directly assess the distribution of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) in the two major subsets of human T cells, we have used limiting dilution microculture systems to determine their frequencies. The two subsets were defined according to their reactivity (or lack thereof) with B9.4 monoclonal antibody (the specificity of which is similar, if not identical, to that of Leu 2b monoclonal antibody). Both B9+ and B9- cells obtained by sorting peripheral blood resting T cells using the fluorescence-activated cell sorter (FACS) were assayed for total CTL-P frequencies in a microculture system that allows clonal growth of every T cell. As assessed by a lectin-dependent assay, approximately 30% of peripheral blood T cells were CTP-P. In the B9+ subset (which represents 20-30% of all T cells), the CTL-P frequency was close to 100%, whereas the B9- subset had a 25-fold lower CTL-P frequency. It is thus evident that 90% and 10% of the total CTL-P in peripheral blood are confined to the B9+ or B9- T cell subsets, respectively. Analysis of the subset distribution of CTL-P directed against a given set of alloantigens confirmed these findings. CTL-P frequencies were also determined in B9+ and B9- subsets derived from T cells that had been activated in allogenic mixed leucocyte cultures (MLC). Approximately 10% of MLC T cells were CTL-P. This frequency was increased 3.5-fold in the B9+ subset, whereas the B9- subset contained only a small, although detectable number of CTL-P. Moreover, the great majority of the (operationally defined) CTL-P in MLC T cell population were found to be directed against the stimulating alloantigens, thus indicating a dramatic increase in specific CTL-P frequencies following in vitro stimulation in bulk cultures.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development

1977 ◽  
Vol 146 (1) ◽  
pp. 91-106 ◽  
Author(s):  
T Hamaoka ◽  
M Yoshizawa ◽  
H Yamamoto ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Development ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell ◽  
Suppressor T Lymphocytes

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

scholarly journals Epiligrin, a component of epithelial basement membranes, is an adhesive ligand for alpha 3 beta 1 positive T lymphocytes.

1993 ◽  
Vol 121 (5) ◽  
pp. 1141-1152 ◽  
Author(s):  
E A Wayner ◽  
S G Gil ◽  
G F Murphy ◽  
M S Wilke ◽  
W G Carter
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Basement Membrane ◽  
B Cell ◽  
Cell Lines ◽  
B Cell Lymphoma ◽  
Lymphokine Activated Killer Cells ◽  
Cutaneous Inflammation ◽  
Epidermal Basement Membrane

The cutaneous T cell lymphomas (CTCL), typified by mycosis fungoides, and several chronic T cell mediated dermatoses are characterized by the migration of T lymphocytes into the epidermis (epidermotropism). Alternatively, other types of cutaneous inflammation (malignant cutaneous B cell lymphoma, CBCL, or lymphocytoma cutis, non-malignant T or B cell type) do not show evidence of epidermotropism. This suggests that certain T lymphocyte subpopulations are able to interact with and penetrate the epidermal basement membrane. We show here that T lymphocytes derived from patients with CTCL (HUT 78 or HUT 102 cells), adhere to the detergent-insoluble extracellular matrix prepared from cultured basal keratinocytes (HFK ECM). HUT cell adhesion to HFK ECM was inhibitable with monoclonal antibodies (mAbs) directed to the alpha 3 (P1B5) or beta 1 (P4C10) integrin receptors, and could be up-regulated by an activating anti-beta 1 mAb (P4G11). An inhibitory mAb, P3H9-2, raised against keratinocytes identified epiligrin as the ligand for alpha 3 beta 1 positive T cells in HFK ECM. Interestingly, two lymphocyte populations could be clearly distinguished relative to expression of alpha 3 beta 1 by flow cytometry analysis. Lymphokine activated killer cells, alloreactive cytotoxic T cells and T cells derived from patients with CTCL expressed high levels of alpha 3 beta 1 (alpha 3 beta 1high). Non-adherent peripheral blood mononuclear cells, acute T or B lymphocytic leukemias, or non-cutaneous T or B lymphocyte cell lines expressed low levels of alpha 3 beta 1 (alpha 3 beta 1low). Resting PBL or alpha 3 beta 1low T or B cell lines did not adhere to HFK ECM or purified epiligrin. However, adhesion to epiligrin could be up-regulated by mAbs which activate the beta 1 subunit indicating that alpha 3 beta 1 activity is a function of expression and affinity. In skin derived from patients with graft-vs.-host (GVH) disease, experimentally induced delayed hypersensitivity reactions, and CTCL, the infiltrating T cells could be stained with mAbs to alpha 3 or beta 1 and were localized in close proximity to the epiligrin-containing basement membrane. Infiltrating lymphocytes in malignant cutaneous B disease (CBCL) did not express alpha 3 beta 1 by immunohistochemical techniques and did not associate with the epidermal basement membrane. The present findings clearly define a function for alpha 3 beta 1 in T cells and strongly suggest that alpha 3 beta 1 interaction with epiligrin may be involved in the pathogenesis of cutaneous inflammation.

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.

scholarly journals Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

1986 ◽  
Vol 163 (5) ◽  
pp. 1037-1050 ◽  
Author(s):  
J H Kehrl ◽  
L M Wakefield ◽  
A B Roberts ◽  
S Jakowlew ◽  
M Alvarez-Mon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Transforming Growth Factor Beta ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Tgf Beta ◽  
Activated T Cells ◽  
Growth Factor Beta

This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.

scholarly journals Improved Specificity of a Multiplex Immunoassay for Quantitation of Anti-Diphtheria Toxin Antibodies with the Use of Diphtheria Toxoid

2011 ◽  
Vol 18 (7) ◽  
pp. 1183-1186 ◽  
Author(s):  
Pieter G. M. van Gageldonk ◽  
Christina von Hunolstein ◽  
Fiona R. M. van der Klis ◽  
Guy A. M. Berbers
Keyword(s):  
Diphtheria Toxin ◽  
Neutralization Test ◽  
Diphtheria Toxoid ◽  
Inhibition Assay ◽  
Nonspecific Binding ◽  
Serum Samples ◽  
Multiplex Immunoassay ◽  
Toxin Binding ◽  
Binding Inhibition ◽  
Binding Inhibition Assay

ABSTRACTA nonspecific binding of antibodies to diphtheria toxin, especially in adult serum samples, was observed in our diphtheria-tetanus-pertussis multiplex immunoassay (DTaP4 MIA). This can be significantly reduced by the use of diphtheria toxoid, achieving a good correlation with the Vero cell neutralization test and the toxin binding inhibition assay.

scholarly journals Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery

2021 ◽  
Vol 12 ◽  
Author(s):  
Eric de Sousa ◽  
Joana R. Lérias ◽  
Antonio Beltran ◽  
Georgia Paraschoudi ◽  
Carolina Condeço ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Leukocyte ◽  
Immune Checkpoint Blockade ◽  
Successful Outcome ◽  
Clinical Samples ◽  
Cancer Tissue ◽  
Rna Seq ◽  
Peripheral T Cells ◽  
Ifn Γ

Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of ‘neoepitope’-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells. TCR αβ-dependent therapies should account for tumor heterogeneity and availability of the TCR repertoire capable of reacting to neoepitopes and functional HLA pathways. Immunogenic epitopes in the tumor-stroma may also be targeted to achieve tumor-containment by changing the immune-contexture in the tumor microenvironment (TME). Non protein-coding regions of the tumor-cell genome may also contain many aberrantly expressed, non-mutated tumor-associated antigens (TAAs) capable of eliciting productive anti-tumor immune responses. Whole-exome sequencing (WES) and/or RNA sequencing (RNA-Seq) of cancer tissue, combined with several layers of bioinformatic analysis is commonly used to predict possible neoepitopes present in clinical samples. At the ImmunoSurgery Unit of the Champalimaud Centre for the Unknown (CCU), a pipeline combining several tools is used for predicting private mutations from WES and RNA-Seq data followed by the construction of synthetic peptides tailored for immunological response assessment reflecting the patient’s tumor mutations, guided by MHC typing. Subsequent immunoassays allow the detection of differential IFN-γ production patterns associated with (intra-tumoral) spatiotemporal differences in TIL or peripheral T-cells versus TIL. These bioinformatics tools, in addition to histopathological assessment, immunological readouts from functional bioassays and deep T-cell ‘adaptome’ analyses, are expected to advance discovery and development of next-generation personalized precision medicine strategies to improve clinical outcomes in cancer in the context of i) anti-tumor vaccination strategies, ii) gauging mutation-reactive T-cell responses in biological therapies and iii) expansion of tumor-reactive T-cells for the cellular treatment of patients with cancer.

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