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Event: 1702

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Suppression of T cell activation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Suppression of T cell activation
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
T cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
immune system

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
IL-1 inhibition KeyEvent Cataia Ives (send email) Open for citation & comment EAGMST Under Review

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
Mus musculus Mus musculus High NCBI
Rattus norvegicus Rattus norvegicus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

T cells are key orchestrators of the response against pathogens and are also fundamental in maintaining self-tolerance. A number of clinically important conditions have been described in which T-cell functions are altered, as in AIDS or upon immunosuppression after application of various immunosuppressive drugs to treat autoimmune disorders or allogeneic graft rejection. T-cell progenitors differentiate in the thymus into immature T cells that acquire the expression of the T-cell receptor (TCR), which recognizes antigen peptides from pathogens presented along with major histocompatibility complex (MHC). In addition to the TCR, T cells are characterized by expression of the co-receptor molecules CD4 and CD8 on their cell surface. CD4+ T cells, also called T helper (Th) cells, recognize antigen/MHC-II complexes on antigen presenting cells (APCs) and coordinate the activation of other immune cells including B cells, macrophages, etc.

Therefore, CD4+ T cells are crucial for coordination of the immune response and for the elimination of invading pathogens. On the other hand, CD8+ T cells, referred to as T cytotoxic cells, recognize antigen/MHC-I complexes and are responsible for the killing of pathogen-infected cells.

T-cell activation and differentiation depends on antigen presenting cells (APCs) such as dendritic cells (DCs), macrophages and B cells. depending on the insult affecting a given tissue. Different subsets of DCs can be generated that in turn are able to coordinate the differentiation of a particular Th subset. To date, the following Th subsets have been described: Th1, Th2, Th9, Th17, Th22, Tfh (follicular helper T cells), Tr1 (type 1regulatory T cells) and Treg (regulatory T cells), each possessing a specific function in the elimination of pathogens. (reviewed by Simeoni et al. (Simeoni et al., 2016))

Although CD4 T cells are able to commit to Th1, Th2 and Th17 lineages in the absence of IL-1R signaling at steady state, these committed CD4 T cells are unable to effectively secrete their cytokines upon TCR ligation. Namely, IL-1 is indispensable for CD4 T cell effector function. (Lin et al, 2015)

Moreover, since full activation of B cells and antibody production and class switch depends on T cell help. The impaired activation of T cells leads to impaired B cell activation and antibody production (reviewed by Mok (Mok, 2010)).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

T cell activation can be evaluated by measuring IL-2 production by ELISA or T cell proliferation by incorporation of the analysis of CFSE labeled T cells or [3H]thymidine incorporation.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

Lin, D., Lei, L., Zhang, Y., et al. (2015), Secreted IL-1alpha promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice. Eur J Immunol 45: 2084-2098, 10.1002/eji.201445195

Mok, M.Y. (2010), The immunological basis of B-cell therapy in systemic lupus erythematosus. Int J Rheum Dis 13: 3-11, 10.1111/j.1756-185X.2009.01458.x

Simeoni, L., Thurm, C., Kritikos, A., et al. (2016), Redox homeostasis, T cells and kidney diseases: three faces in the dark. Clin Kidney J 9: 1-10, 10.1093/ckj/sfv135

Weih, F., Carrasco, D., Durham, S.K., et al. (1995), Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 80: 331-340,