Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants

Nature ◽  
1994 ◽  
Vol 369 (6479) ◽  
pp. 403-407 ◽  
Author(s):  
Paul Klenerman ◽  
Sarah Rowland-Jones ◽  
Steve McAdam ◽  
Jon Edwards ◽  
Susan Daenke ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Naturally Occurring ◽  
Hiv 1

scholarly journals Bulk Culture Levels of Specific Cytotoxic T-Cell Activity Against HIV-1 Proteins are not Associated with Risk of Death

1999 ◽  
Vol 50 (2) ◽  
pp. 223-227 ◽  
Author(s):  
Aladdin ◽  
Ullum ◽  
Cozzi Lepri ◽  
Leffers ◽  
Katzenstein ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Risk Of Death ◽  
Hiv 1 ◽  
Bulk Culture

The influence of lymphocyte counts and disease progression on circulating and inducible anti-HIV-1 cytotoxic T-cell activity in HIV-1-infected subjects

AIDS ◽  
1992 ◽  
Vol 6 (10) ◽  
pp. 1085-1094 ◽  
Author(s):  
Michael D. Grant ◽  
Fiona M. Smaill ◽  
Dharam P. Singal ◽  
Kenneth L. Rosenthal
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals A biomimetic assay platform for the interrogation of antigen-dependent anti-tumor T-cell function

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jeremy To ◽  
Doug Quackenbush ◽  
Emily Rowell ◽  
Lilin Li ◽  
Connor Reed ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Dependent Manner ◽  
Cyclin Dependent Kinase ◽  
Histocompatibility Complex ◽  
T Cell Function ◽  
Cytolytic Granule ◽  
Screening Platform

AbstractOvercoming tumor-mediated immunosuppression and enhancing cytotoxic T-cell activity within the tumor microenvironment are two central goals of immuno-oncology (IO) drug discovery initiatives. However, exploratory assays involving immune components are often plagued by low-throughput and poor clinical relevance. Here we present an innovative ultra-high-content assay platform for interrogating T-cell-mediated killing of 3D multicellular tumor spheroids. Employing this assay platform in a chemical genomics screen of 1800 annotated compounds enabled identification of small molecule perturbagens capable of enhancing cytotoxic CD8+ T-cell activity in an antigen-dependent manner. Specifically, cyclin-dependent kinase (CDK) and bromodomain (BRD) protein inhibitors were shown to significantly augment anti-tumor T-cell function by increasing cytolytic granule and type II interferon secretion in T-cells in addition to upregulating major histocompatibility complex (MHC) expression and antigen presentation in tumor cells. The described biotechnology screening platform yields multi-parametric, clinically-relevant data and can be employed kinetically for the discovery of first-in-class IO therapeutic agents.

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

scholarly journals Skin test to assess virus-specific cytotoxic T-cell activity.

1992 ◽  
Vol 89 (16) ◽  
pp. 7757-7761 ◽  
Author(s):  
T. M. Kundig ◽  
A. Althage ◽  
H. Hengartner ◽  
R. M. Zinkernagel
Keyword(s):  
T Cell ◽  
Skin Test ◽  
Cell Activity ◽  
Cytotoxic T Cell

scholarly journals Radiotherapy and cisplatin increase immunotherapy efficacy by enabling local and systemic intratumoral T-cell activity

2018 ◽  
Author(s):  
Paula Kroon ◽  
Elselien Frijlink ◽  
Victoria Iglesias-Guimarais ◽  
Andriy Volkov ◽  
Marit M van Buuren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Tumor Control ◽  
Cancer Treatments ◽  
Costimulatory Receptor ◽  
Breast Cancer Model ◽  
Mouse Breast Cancer ◽  
Summary Statement

AbstractTo increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined in a poorly immunogenic mouse breast cancer model the potential of antibody-based immunomodulation and conventional anti-cancer treatments to collaborate with anti-PD-1 treatment. One important requirement to improve anti-PD-1-mediated tumor control was to promote tumor-specific cytotoxic T cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1-unrelated mechanisms of CTL suppression in the tumor micro-environment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1-targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.Summary statementThis study reveals that radiotherapy and cisplatin can be ‘re-purposed’ to improve antibody-based immunotherapy success in poorly immunogenic breast cancer by overruling PD-1 unrelated mechanisms of T cell suppression in the tumor micro-environment.

CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity

2019 ◽  
Vol 11 (508) ◽  
pp. eaax8861 ◽  
Author(s):  
Ji Li ◽  
Robert Piskol ◽  
Ryan Ybarra ◽  
Ying-Jiun J. Chen ◽  
Jason Li ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Bispecific Antibody ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Cytolytic Activity ◽  
Cytotoxic T Cell ◽  
Cytokine Release ◽  
Initial Exposure ◽  
Tnf Α

T cell–retargeting therapies have transformed the therapeutic landscape of oncology. Regardless of the modality, T cell activating therapies are commonly accompanied by systemic cytokine release, which can progress to deadly cytokine release syndrome (CRS). Because of incomplete mechanistic understanding of the relationship between T cell activation and systemic cytokine release, optimal toxicity management that retains full therapeutic potential remains unclear. Here, we report the cell type–specific cellular mechanisms that link CD3 bispecific antibody–mediated killing to toxic cytokine release. The immunologic cascade is initiated by T cell triggering, whereas monocytes and macrophages are the primary source of systemic toxic cytokine release. We demonstrate that T cell–generated tumor necrosis factor–α (TNF-α) is the primary mechanism mediating monocyte activation and systemic cytokine release after CD3 bispecific treatment. Prevention of TNF-α release is sufficient to impair systemic release of monocyte cytokines without affecting antitumor efficacy. Systemic cytokine release is only observed upon initial exposure to CD3 bispecific antibody not subsequent doses, indicating a biological distinction between doses. Despite impaired cytokine release after second exposure, T cell cytotoxicity remained unaffected, demonstrating that cytolytic activity of T cells can be achieved in the absence of cytokine release. The mechanistic uncoupling of toxic cytokines and T cell cytolytic activity in the context of CD3 bispecifics provides a biological rationale to clinically explore preventative treatment approaches to mitigate toxicity.

scholarly journals Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and high cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D.

1985 ◽  
Vol 162 (6) ◽  
pp. 2125-2141 ◽  
Author(s):  
R M Zinkernagel ◽  
T Leist ◽  
H Hengartner ◽  
A Althage
Keyword(s):  
T Cell ◽  
Virus Isolate ◽  
Cell Activity ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Time To Death ◽  
Virus Isolates ◽  
Susceptibility Patterns

The lymphocytic choriomeningitis virus (LCMV) isolates Docile (D) and Aggressive (A) of Pfau et al. were studied in various strains of mice. Disease susceptibility, assessed as mortality and time to death to LCMV-D or -A varied greatly amongst mouse strains, and all four possible susceptibility patterns were observed: susceptibility to both (e.g. SWR/J), resistance to both (e.g. DBA/2), susceptibility to A but resistance to D (C57BL/6), or vice versa (CBA/J). Irrespective of the virus isolate or the mouse strain tested, susceptibility correlated with both early and high cytotoxic T cell activity found in spleens or leptomeningeal infiltrates, and with early and high primary footpad swelling reaction after local infection. C57BL/6 mice infected with A or SWR/J infected with A or with D showed, in both test systems, early and high activities; in contrast, DBA/2 mice infected with either D or A, and C57BL/6 infected with D showed no or only slow and low responses in both tests. Early and high LCMV-specific cytotoxic T cell activity, and the rapidity and extent of the primary footpad reaction directly correlated with susceptibility to LCM and all were dominantly regulated by H-2D.

Viral peptides that interact with HLA-A2 inhibit cytotoxic T cell activity

1988 ◽  
Vol 23 (2) ◽  
pp. 139
Author(s):  
P.A. Robbins ◽  
A.J. McMichael
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell
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