Ca2+ Signals in CD4+ T Cells during Early Contacts with Antigen-Bearing Dendritic Cells in Lymph Node

Wei, Sindy H.; Safrina, Olga; Yu, Ying; Garrod, Kym R.; Cahalan, Michael D.; Parker, Ian

doi:10.4049/jimmunol.179.3.1586

Cited by 82 publications

(89 citation statements)

References 52 publications

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“…Most studies have explored calcium responses by introducing T cells loaded with small-molecular fluorochrome indicators in vivo and imaging lymph node explants (32,33). In line with our observation (Fig.…”

Section: Discussionsupporting

confidence: 89%

Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy

Kyratsous

Bauer

Zhang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT. In vitro activated T cells first settle in secondary (2°) lymphatic tissues (e.g., the spleen) where, in the absence of autoantigen, they establish transient contacts with stroma cells as indicated by sporadic short-lived calcium spikes. The T cells then exit the spleen for the CNS where they first roll and crawl along the luminal surface of leptomeningeal vessels without showing calcium activity. Having crossed the blood-brain barrier, the T cells scan the leptomeningeal space for autoantigen-presenting cells (APCs). Sustained contacts result in long-lasting calcium activity and NFAT translocation, a measure of full T-cell activation. This process is sensitive to anti-MHC class II antibodies. Importantly, the capacity to activate T cells is not a general property of all leptomeningeal phagocytes, but varies between individual APCs. Our results identify distinct checkpoints of T-cell activation, controlling the capacity of myelin-specific T cells to invade and attack the CNS. These processes may be valuable therapeutic targets.autoimmunity | intracellular calcium | T-cell activation | central nervous system | two-photon imaging

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Section: Discussionsupporting

confidence: 89%

Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy

Kyratsous

Bauer

Zhang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…In order to efficiently generate sustained signals necessary for cell activation, lymphocytes must change from an actively motile state to stop crawling when they encounter an APC. This has been shown for T cells where encounter with an APC induce a quick, transient Ca 2+ influx in the T cell, which in turn results in reduced motility [38]. Our data demonstrate that calcium mobilization is a functional property of the NKR-P1F receptor as well as NKR-P1A, although less powerful.…”

supporting

confidence: 63%

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca 2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A + T cells in all tissues analyzed, and by many NKR-P1A − intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A + and NKR-P1F + cells was high at birth and thereafter declined, while NKR-P1B + and NKR-P1G + cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.Keywords: C-type lectin-related molecules r NK-cell receptors r NKR-P1 r Rodent Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNatural killer (NK) cells are innate lymphoid cells with the ability to eliminate virally infected cells and transformed or allogeneic cells. They produce cytokines early in the immune response, and play an important role in shaping the immune response, e.g. in the context of inflammation and transplantation. These tasks are controlled by a wide range of receptors with different functions and ligands, such as Ly49 receptors, which recognize both classical and nonclassical MHC class I molecules, as well as MHC Correspondence: Dr. Lise Kveberg e-mail: lise.kveberg@rr-research.no class I-like virally encoded ligands [1][2][3]. Another family of MHCbinding receptors is the conserved NKG2/CD94 heterodimers, which bind the nonclassical MHC molecule HLA-E in human [4], its rodent homologue Qa-1 b in the mouse [5,6] and RT.BM1 in the rat [7]. Both the Ly49 and NKG2/CD94 receptor families contain inhibitory and activating members. NKG2D is a promiscuous activating receptor, recognizing several MHC class I-related ligands frequently upregulated upon cellular stress and associated with viral infection and malignant transformation [8].The activating NK cytotoxicity receptors react with several virus-derived and endogenous ligands [9,10].One of the earliest NK-cell receptors to be characterized was the NK-cell receptor protein 1A (NKR-P1A) in the rat, which is C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 502Lise Kveberg et al. Eur. J. Immunol. 2015. 45: 501-...

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“…Later, several studies found that relatively high concentrations of antigen can induce rapid or immediate arrest of transgenic T cells on DCs without an initial phase of T-cell screening. [6][7][8] These data would suggest that T-cell screening of DCs is not obligatory when antigen is abundant. 9 However, the relevance of these findings to immunity with diverse T-cell repertoires is not clear.…”

Section: Introductionmentioning

confidence: 98%

Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD

Lin

Fulton²,

Berginski

et al. 2014

Blood

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Ca2+ Signals in CD4+ T Cells during Early Contacts with Antigen-Bearing Dendritic Cells in Lymph Node

Cited by 82 publications

References 52 publications

Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy

Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD

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