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Event: 983

Key Event Title

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

Suppression, Suppression of T-cell dependent antibody response (TDAR)

Short name
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Suppression, Suppression of T-cell dependent antibody response (TDAR)
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Biological Context

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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

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

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

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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

Life Stages

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Sex Applicability

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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

FK506 is known to suppress T-cell dependent antibody response; however, it has not been reported so far to directly affect B-cells on antibody production. FK506 inhibits the production of multiple classes of cytokines by T cells; among them, IL-4 and IL-13 are B-cell stimulating factors to proliferate, stimulate B cells, and to activate and induce class switch. Suppression of such B-cell-related cytokines deems to be the main factor for the suppression of TDAR by FK506.

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

In vitro: T and B cells isolated from human PBMC were co-cultured with FK506 for 9 days in the presence of polyclonal T cell stimulation, after which supernatants were tested for immunoglobulin IgM and IgG levels by sandwich ELISA (Heidt et al, 2009). Human PBMC were stimulated with anti-CD3/CD28 for 24 h in the presence of FK506. IL-6 produced in the culture supernatants was measured using ELISA (Sakuma et al. 2001b). SKW6.4 cells were cultured with anti-CD3/CD28 stimulated PBMC culture supernatant. After 4 days culture, IgM produced in the culture supernatants was measured by ELISA (Sakuma et al. 2001b). In vivo: Rats are repeated-administered FK506 orally and immunized by KLH, and its serum is examined for T cell-dependent antigen-specific IgM and IgG levels by sandwich ELISA. Mice are repeated-administered FK506 orally and immunized by SRBC, and its spleen cells are examined by plaque forming cell assay (Heidt et al, 2009, Kino et al. 1987, Ulrich et al. 2004). Class switch: T cells derived from human PBMCs were cultured with FK506, and cytokine mRNA levels of B cell stimulatory cytokines such as IFN-gamma, IL-2, IL-4, IL-5, IL-10, and IL-13 produced by T cells are measured by quantitative PCR (Ulrich et al. 2004).

Domain of Applicability

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

In the in vitro experiment using peripheral blood mononuclear cells from blood-bank donors, treatment with FK506 revealed to suppress the production of immunoglobulin (Ig) M and G antibodies specific to T-cell dependent antigens (Heidt et al, 2009), and, in human PBMC cultures, FK506 suppressed the production of IL-6 and IgM antibodies in the presence of T-cell activation (Sakuma et al. 2001b). Oral administration of FK506 to mice for 4 days suppresses the response of plaque forming cells (PFC) using splenocyte after intravenous immunization of sheep erythrocytes (Kino et al. 1987). Oral administration of FK506 to rats over a four-week period reduced production of both anti-KLH-IgG and IgM antibodies after subcutaneous immunization of KLH (Ulrich et al. 2004).

References

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

[1] Heidt, S., Roelen, D. L., Eijsink, C., Eikmans, M., van Kooten, C., Claas, F. H. and Mulder, A. (2010). Calcineurin inhibitors affect B cell antibody responses indirectly by interfering with T cell help. Clinical and experimental immunology. 159(2): 199-207.

[2] Sakuma, S., Kato, Y., Nishigaki, F., Magari, K., Miyata, S., Ohkubo, Y., and Goto, T. (2001b). Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro. International Immunopharmacology 1(4): 749-57.

[3] Kino, T., Hatanaka, H., Hashimoto, M., Nishiyama, M., Goto, T., Okuhara, M., Kohsaka, M., Aoki, H. and Imanaka, H. (1987). FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. Journal of antibiotics. 40(9): 1249-1255.

[4] Ulrich, P., Paul, G., Perentes, E., Mahl, A., and Roman D. (2004). Validation of immune function testing during a 4-week oral toxicity study with FK506. Toxicology Letters 149(1-3): 123-31.