Multichannel Fluorescence Spinning Disk Microscopy Reveals Early Endogenous CD4 T Cell Recruitment in Contact Sensitivity via Complement

Norman, M. Ursula; Hulliger, Sara; Colarusso, Pina; Kubes, Paul

doi:10.4049/jimmunol.180.1.510

Cited by 34 publications

(44 citation statements)

References 42 publications

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“…As previously described, 24 h after a single challenge, leukocyte adhesion was significantly elevated above basal levels, with the adherent leukocyte population comprising numerous neutrophils, with less frequent CD4 + and CD8 + T cells ( Fig. 2A) (28,39). At this time point, adhesion of CD4 + T cells was significantly increased in AnxA1 2/2 mice relative to WT mice, whereas adhesion of CD8 + T cells and neutrophils was comparable (Fig.…”

Section: Anxa1 Deficiency Increases Adhesion Of T Cells and Neutrophisupporting

confidence: 52%

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Yang

Song

Deane

et al. 2013

The Journal of Immunology

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Annexin A1 (AnxA1) is recognized as an endogenous anti-inflammatory molecule. However, its effects on the adaptive immune response and, in particular, on T cells remain unclear. In this study, we investigated the actions of AnxA1 in three distinct models of T cell–mediated inflammation. In contact hypersensitivity, collagen-induced arthritis, and inflammation induced by OT-II TCR transgenic T cells responding to OVA, AnxA1 deficiency significantly increased Ag-induced T cell proliferation and the resultant level of inflammation. In the contact hypersensitivity model, this was associated with increased adhesion of CD4+ T cells, CD8+ T cells, and neutrophils in the dermal microvasculature, as well as increased T cell expression of RORγt and IL-17A. In collagen-induced arthritis, deficiency of endogenous AnxA1 increased susceptibility to arthritis and Ag-specific T cell activation. Deficiency of AnxA1 also increased OVA-induced cutaneous delayed-type hypersensitivity and IFN-γ and IL-17 release. Transfer experiments using CD4+ T cells from AnxA1−/− mice demonstrated that the absence of AnxA1 solely in T cells resulted in increased inflammatory responses in wild-type recipients. Similarly, experiments using AnxA1−/− OT-II CD4+ T cells demonstrated that the absence of AnxA1 in T cells was sufficient to induce increased Ag-specific CD4+ T cell proliferation in vivo, augment T cell production of IFN-γ, IL-17, TNF, and IL-6, and increase Akt, ERK, and p38 activation. Together, these findings indicate that T cell–expressed AnxA1 functions to attenuate T cell–driven inflammatory responses via T cell–intrinsic effects on intracellular signaling, proliferation, and Th1/Th17 cytokine release.

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Section: Anxa1 Deficiency Increases Adhesion Of T Cells and Neutrophisupporting

confidence: 52%

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Yang

Song

Deane

et al. 2013

The Journal of Immunology

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“…In previous work, we have used intravital microscopy of the dermal microvasculature in flank skin to demonstrate that CD4 + T cells represent only a minor proportion of the total number of interacting leukocytes during the CS response (35). In experiments focusing on recruitment of these infrequent leukocyte subsets, examination of the flank skin affords the advantage over the more common ear skin preparation of allowing visualization of at least 10 postcapillary venules in each preparation, facilitating robust quantitative analysis of adhesion of these low-frequency subsets.…”

Section: Resultsmentioning

confidence: 99%

“…CS was induced as previously described (35). Briefly, mice were sensitized by the application of 50 ml 5% oxazolone (Sigma-Aldrich, St. Louis, MO) in an acetone/olive oil vehicle (4:1) to a shaved patch on the back.…”

Section: Oxazolone-induced Model Of Contact Sensitivitymentioning

confidence: 99%

“…Intravital microscopy of the dermal microvasculature of the flank Skin on the flank was surgically prepared for standard epifluorescence and confocal intravital microscopy as previously described (35). Mice were anesthetized (ketamine hydrochloride, 150 mg/kg; xylazine hydrochloride, 10 mg/kg) and a heat pad was used to maintain body temperature.…”

Section: Histologymentioning

confidence: 99%

“…Specific leukocyte subset adhesion. To examine adhesion of specific leukocyte subsets, confocal intravital microscopy was used (35,36). To enable identification of specific leukocyte subsets, mice received the following Abs (eBioscience, San Diego, CA): anti-Gr-1-PE (0.8 mg) to label neutrophils, and anti-CD4-FITC (2 mg) and anti-CD8-allophycocyanin (2 mg) to label CD4 + and CD8 + cells, respectively, administered i.v.…”

Section: Histologymentioning

confidence: 99%

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Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion

Deane

Abeynaike

Norman

et al. 2012

The Journal of Immunology

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Regulatory T cells (Tregs) must express appropriate skin-homing adhesion molecules to exert suppressive effects on dermal inflammation. However, the mechanisms whereby they control local inflammation remain unclear. In this study we used confocal intravital microscopy in wild-type and Foxp3-GFP mice to examine adhesion of effector T cells and Tregs in dermal venules. These experiments examined a two-challenge model of contact sensitivity (CS) in which Treg abundance in the skin progressively increases during the course of the response. Adhesion of CD4+ T cells increased during CS, peaking 8–24 h after an initial hapten challenge, and within 4 h of a second challenge. At these time points, 40% of adherent CD4+ T cells were Foxp3+ Tregs. CD4+ T cell adhesion was highly dependent on ICAM-1, and consistent with this finding, anti–ICAM-1 prevented Treg adhesion. Skin TGF-β levels were elevated in skin during both challenges, in parallel with Treg adhesion. In the two-challenge CS model, inhibition of ICAM-1 eliminated Treg adhesion, an effect associated with a significant increase in neutrophil adhesion. Similarly, total CD4+ T cell depletion caused an increase in adhesion of CD8+ T cells. Because Treg adhesion was restricted by both of these treatments, these experiments suggest that adherent Tregs can control adhesion of proinflammatory leukocytes in vivo. Moreover, the critical role of ICAM-1 in Treg adhesion provides a potential explanation for the exacerbation of inflammation reported in some studies of ICAM-1–deficient mice.

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Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration

et al. 2013

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Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37 −/− mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37 −/− mice coincides with a striking failure to induce antigenspecific IFN-γ-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemotactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naïve T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37 −/− mice.Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37 −/− mice is impaired DC migration. Keywords: CD37 r Cellular immunity r Dendritic cells r Migration r TetraspaninsAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAdaptive cellular immunity is initiated by presentation of foreign antigen by DCs to antigen-specific naïve T lymphocytes. DCs exist sparsely in peripheral tissues in a state specialized for antigen uptake and processing. However, upon pathogen encounter, DCsCorrespondence: Dr. Mark D. Wright e-mail: Mark.Wright@monash.edu transduce signals through pattern recognition receptors, leading to an increased expression of cell surface molecules and cytokines, and induction of DC migration from the periphery to draining lymph nodes (DLNs) via afferent lymphatic vessels. Thus, upon their arrival in secondary lymphoid organs, DCs are equipped to initiate adaptive cellular immune responses through their ability to * These authors contributed equally to this work.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 1208-1219 Cellular immune response 1209 activate naïve antigen-specific T cells [1]. Despite the importance of DC migration from the periphery to DLNs, the roles of the numerous molecules that regulate this process are incompletely understood. One such molecule is the leukocyte-specific membrane protein CD37, a member of the tetraspanin protein superfamily. Tetraspanins molecularly organize cellular membranes by interactions with partner molecules, which they direct into regulated signal-transducing tetraspanin-enriched microdomains. The cellular processes regulated by tetraspanin-mediated molecular organization include proliferation, adhesion and migration [2,3]. In immune cells, many important cell s...

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Multichannel Fluorescence Spinning Disk Microscopy Reveals Early Endogenous CD4 T Cell Recruitment in Contact Sensitivity via Complement

Cited by 34 publications

References 42 publications

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion

Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration

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