Chemokines Fail to Up-Regulate β1 Integrin-Dependent Adhesion in Human Th2 T Lymphocytes

Clissi, Barbara; D’Ambrosio, Daniele; Geginat, Jens; Colantonio, Lucia; Morrot, Alexander; Freshney, Norman W.; Downward, Julian; Sinigaglia, Francesco; Pardi, Ruggero

doi:10.4049/jimmunol.164.6.3292

Cited by 30 publications

(26 citation statements)

References 47 publications

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“…Indeed, we found that antibody-induced crosslinking of CD44 resulted in a 2.3-fold increase in the binding of Th1 cells to recombinant ICAM-1, confirming that CD44-derived signaling modulates T-cell adhesive properties ( Figure 4C). This modulation is comparable to that induced after crosslinking of PSGL-1 37 or by chemokines, 38 suggesting a cooperation of selectins and chemokines for Th1 cell arrest.…”

Section: Cd44 Is An E-selectin Ligand On T Cells 2441supporting

confidence: 58%

Physiological Contribution of CD44 as a Ligand for E-Selectin during Inflammatory T-Cell Recruitment

Nácher

Blázquez

Shao

et al. 2011

The American Journal of Pathology

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Endothelial selectins guide the migration of inflammatory T cells to extralymphoid tissues. Whereas Pselectin glycoprotein ligand-1 (PSGL-1) functions as the exclusive ligand for P-selectin, it acts in coordination with additional glycoproteins to mediate Eselectin binding. CD44 can act as one such ligand in neutrophils, but its contribution in inflammatory T lymphocytes remains unexplored. We have used realtime in vivo imaging of the cremasteric and dermal microcirculations to explore the dynamics of leukocyte recruitment, as well as the physiological contribution of CD44 in a model of Th1-driven inflammation. CD4؉ T-cell rolling frequency and kinetics, as well as arrest, were dependent on endothelial selectins and were markedly altered under inflammatory conditions. CD44 extracted from Th1 cells bound to soluble E-selectin in vitro and cooperated with PSGL-1 by controlling rolling velocities and promoting firm arrest. Using several competitive recruitment assays in a delayed-type hypersensitivity model, we show that the combined absence of CD44 and PSGL-1 impairs inflammatory T-cell recruitment beyond that of PSGL-1 alone. Differential expression of leukocyte fucosyltransferases in these cells may account for the differential use of E-selectin ligands relative to neutrophils. Our results identify additional mechanisms by which CD44 modulates the inflammatory response. The trafficking of T lymphocytes is regulated by their repertoire of adhesion and chemotactic receptors. Naïve T cells recirculate through secondary lymphoid organs in search of their cognate antigen, a process facilitated by their specific binding to high endothelial venules through L-selectin, ␤2 integrins, and the chemokine receptor CCR7. Once activated, effector and memory T cells switch their adhesive and signaling repertoire to one that allows immune surveillance of tissues. In particular, skin and inflamed areas are dynamically infiltrated by activated T cells, a process that underlies a number of pathogenic inflammatory diseases.1 It is generally accepted that this infiltration is initiated by extravasation from the blood microvasculature through a multistep cascade similar to that undergone by neutrophils, including initial tethering and rolling events followed by firm arrest and diapedesis.2 Tethering and rolling are initiated by labile interactions mediated by endothelial P-and E-selectins (encoded by Selp and Sele genes, respectively) expressed constitutively in the skin microvasculature 3 and induced in other tissues during inflammation.2 Induction of ligands for endothelial selectins is therefore critical for the acquired migrating properties of inflammatory lymphocytes. 4 Two glycoproteins expressed on Th1 lymphocytes, Pselecting glycoprotein ligand-1 (PSGL-1; encoded by Selplg) and the sialomucin CD43, have been shown to

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Section: Cd44 Is An E-selectin Ligand On T Cells 2441supporting

confidence: 58%

Physiological Contribution of CD44 as a Ligand for E-Selectin during Inflammatory T-Cell Recruitment

Nácher

Blázquez

Shao

et al. 2011

The American Journal of Pathology

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“…This suggests that clustering of integrins is at least partially dependent on the presence of a suitable integrin ligand. Although differential regulation of ␤ 1 vs ␤ 2 integrin function in T cells by chemokines is possible under some conditions (35,36), our experiments demonstrated similar clustering of ␣ 1 and ␤ 2 integrins on the cell surface in response to CCL20 as long as both VCAM-1 and ICAM-1, respectively, were immobilized on the plate.…”

Section: Discussionmentioning

confidence: 56%

CCR6 Colocalizes with CD18 and Enhances Adhesion to Activated Endothelial Cells in CCR6-Transduced Jurkat T Cells

Maki¹,

Morales²,

Carroll³

et al. 2002

The Journal of Immunology

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CCR6 is expressed by memory T cells (mTC) and is a requirement for efficient arrest of a subset of mTC to activated human dermal microvascular endothelial cells (HDMEC) under physiologic shear stress. We now address whether CCR6 alone is sufficient to induce arrest of a model T cell line (Jurkat) that shows low expression of all CCRs tested (CCR1–10). Herein, we transduced Jurkat (JK) T cells expressing fucosyltransferase VII with a chimeric chemokine receptor consisting of CCR6 fused to enhanced green fluorescent protein. In contrast to the starting JK lines, the resulting cell line (JK fucosyltransferase VII-CCR6) migrated 6-fold better to CCL20 in chemotaxis assays, arrested in response to CCL20 that was immobilized to plastic, and demonstrated a 2.5-fold increase in adhesion to activated HDMEC (p = 0.001). Adhesion was blocked by anti-CD18 mAb (p = 0.005) but not by anti-CD49d mAb (p = 0.3). After arrest on recombinant substrates, CCR6 clustered on the surface as detected by real-time observation of enhanced green fluorescent protein fluorescence. Dual-label confocal microscopy revealed that LFA-1 (CD18 and CD11a), but not CXCR4, colocalized with clustered CCR6 in the presence of immobilized CCL20. Thus, the functional expression of CCR6 is sufficient to provide the chemokine signaling necessary to induce arrest of a JK T cell line to activated HDMEC. Clustering of CCR6 and coassociation with critical integrins may serve to strengthen adhesion between T cells and activated endothelial cells.

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“…In addition to PSGL-1, certain integrins likely to be important for passage across the endothelium have also been reported to be differentially expressed on Th1 and Th2 cells (72,73). We have shown ␣ L ␤ 2 (LFA-1), a receptor for ICAM-1, at higher levels on IFN-␥-producing, Th1-like cells.…”

Section: Discussionmentioning

confidence: 68%

Recruitment of IFN-γ-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions

Manivannan

Jiang

et al. 2004

The Journal of Immunology

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Although there is evidence that altering the Th1/Th2 balance toward Th2 cells may be important in the resolution of Th1-type autoimmune disease, adoptive transfer of Th2 cells is not effective in protecting against Th1-type disease and may cause disease. Therefore, we examined the recruitment of Th1- and Th2-like cells into the retina in the murine autoimmune disease experimental autoimmune uveoretinitis. CD4 T cells were polarized in vitro to IFN-γ-producing Th1-like cells and non-IFN-γ-producing Th2-like cells, labeled, and adoptively transferred. Trafficking to the retina in vivo was evaluated by scanning laser ophthalmoscopy and infiltration by confocal microscopy. There were more rolling and adherent Th1-like cells and they rolled more slowly than did Th2-like cells. Th1-like cells were preferentially recruited into the retinal parenchyma at both initiation and resolution. Surface P-selectin glycoprotein ligand 1 (PSGL-1) and LFA-1 were up-regulated on both populations but were expressed at higher levels on Th1-like cells. Up-regulation of CD44 expression was higher on Th2-like cells. P-selectin, E-selectin, and ICAM-1 are up-regulated on postcapillary venules in the retina. Pretreatment of Th1-like cells with anti-PSGL-1 inhibited rolling and infiltration of Th1-like cells but not Th2-like cells, providing direct in vivo evidence for the inability of Th2 to respond to P/E-selectin despite increased expression of PSGL-1. Anti-LFA-1 pretreatment inhibited infiltration of both Th1- and Th2-like cells, but more so Th-1. We suggest that random trafficking of activated T cells (both Th1 and Th2) across the blood-retina barrier is mediated by CD44:CD44R and LFA-1:ICAM-1, whereas preferential recruitment of Th1 cells is mediated by PSGL-1:P/E-selectin.

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Chemokines Fail to Up-Regulate β1 Integrin-Dependent Adhesion in Human Th2 T Lymphocytes

Cited by 30 publications

References 47 publications

Physiological Contribution of CD44 as a Ligand for E-Selectin during Inflammatory T-Cell Recruitment

Physiological Contribution of CD44 as a Ligand for E-Selectin during Inflammatory T-Cell Recruitment

CCR6 Colocalizes with CD18 and Enhances Adhesion to Activated Endothelial Cells in CCR6-Transduced Jurkat T Cells

Recruitment of IFN-γ-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions

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