scholarly journals ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands.

1994 ◽  
Vol 127 (3) ◽  
pp. 867-878 ◽  
Author(s):  
M R Campanero ◽  
P Sánchez-Mateos ◽  
M A del Pozo ◽  
F Sánchez-Madrid
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Adhesion Molecule ◽  
Contact Area ◽  
Phorbol Esters ◽  
Jurkat Cells ◽  
The Other ◽  
Intercellular Adhesion Molecule ◽  
Cell Contact ◽  
Beta 1 Integrin

Leukocyte activation is a complex process that involves multiple cross-regulated cell adhesion events. In this report, we investigated the role of intercellular adhesion molecule-3 (ICAM-3), the third identified ligand for the beta 2 integrin leukocyte function-associated antigen-1 (LFA-1), in the regulation of leukocyte adhesion to ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and the 38- and 80-kD fragments of fibronectin (FN40 and FN80). The activating anti-ICAM-3 HP2/19, but not other anti-ICAM-3 mAb, was able to enhance T lymphoblast adhesion to these proteins when combined with very low doses of anti-CD3 mAb, which were unable by themselves to induce this phenomenon. In contrast, anti-ICAM-1 mAb did not enhance T cell attachment to these substrata. T cell adhesion to ICAM-1, VCAM-1, FN40, and FN80 was specifically blocked by anti-LFA-1, anti-VLA alpha 4, and anti-VLA alpha 5 mAb, respectively. The activating anti-ICAM-3 HP2/19 was also able to specifically enhance the VLA-4- and VLA-5-mediated binding of leukemic T Jurkat cells to VCAM-1, FN40, and FN80, even in the absence of cooccupancy of the CD3-TcR complex. We also studied the localization of ICAM-3, LFA-1, and the VLA beta 1 integrin, by immunofluorescence microscopy, on cells interacting with ICAM-1, VCAM-1 and FN80. We found that the anti-ICAM-3 HP2/19 mAb specifically promoted a dramatic change on the morphology of T lymphoblasts when these cells were allowed to interact with those adhesion ligands. Under these conditions, it was observed that a large cell contact area from which an uropod-like structure (heading uropod) was projected toward the outer milieu. However, when T blasts were stimulated with other adhesion promoting agents as the activating anti-VLA beta 1 TS2/16 mAb or phorbol esters, this structure was not detected. The anti-ICAM-3 TP1/24 mAb was also unable to induce this phenomenon. Notably, a striking cell redistribution of ICAM-3 was induced specifically by the HP2/19 mAb, but not by the other anti-ICAM-3 mAb or the other adhesion promoting agents. Thus, ICAM-3 was almost exclusively concentrated in the most distal portion of the heading uropod whereas either LFA-1 or the VLA beta 1 integrin were uniformly distributed all over the large contact area. Moreover, this phenomenon was also observed when T cells were specifically stimulated with the HP2/19 mAb to interact with TNF alpha-activated endothelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Activation of Peripheral Blood T Cells by Interaction and Migration Through Endothelium: Role of Lymphocyte Function Antigen-1/Intercellular Adhesion Molecule-1 and Interleukin-15

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 886-896 ◽  
Author(s):  
David Sancho ◽  
Marı́a Yáñez-Mó ◽  
Reyes Tejedor ◽  
Francisco Sánchez-Madrid
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
T Cell Activation ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Cell Subset ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Ifn Γ

Abstract Cell adhesion molecules have a key role in the migration of T cells to inflammatory foci. However, the effect of the endothelial-lymphocyte interaction on the activation of the latter cells remains unresolved. We have studied the effect of resting and stimulated endothelial cells (ECs) on the activation of peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25 activation antigens. The incubation of PBTLs with tumor necrosis factor-–activated EC monolayers, either alive or fixed, induced the expression of CD69 but not CD25, preferentially in the CD8+CD45RO+ cell subset. Furthermore, it induced the production of cytokines such as IFN-γ, but not that of interleukin-2 (IL-2) and IL-4. EC treated with other stimuli such as IL-1β, IFN-γ, or lipopolysaccharide also showed the same proactivatory effect on T cells. Lymphocyte activation was almost completely inhibited by blocking anti-CD18 and anti–intercellular adhesion molecule-1 (anti–ICAM-1) monoclonal antibodies (MoAbs), but only slightly affected by MoAbs against CD49d, vascular cell adhesion molecule-1, and anti–IL-15. In addition, the interaction of PBTL with immobilized ICAM-1 induced CD69 expression in the same memory T-cell subset. IL-15 induced T-cell activation with expression of CD69 and CD25, and production of IFN-γ, and its effect was additive with that triggered by cell adhesion to either EC or immobilized ICAM-1. The transmigration of PBTLs through either confluent EC monolayers or ICAM-1–coated membranes also induced efficiently the expression of CD69. When IL-15 was used as chemoattractant in these assays, a further enhancement in CD69 expression was observed in migrated cells. Together these results indicate that stimulated endothelium may have an important role in T-cell activation, through the lymphocyte function antigen-1/ICAM-1 pathway, and that IL-15 efficiently cooperates in this phenomenon. These observations could account for the abundance of CD69+ cells in the lymphocytic infiltrates of several chronic inflammatory diseases.

Activation of Peripheral Blood T Cells by Interaction and Migration Through Endothelium: Role of Lymphocyte Function Antigen-1/Intercellular Adhesion Molecule-1 and Interleukin-15

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 886-896 ◽  
Author(s):  
David Sancho ◽  
Marı́a Yáñez-Mó ◽  
Reyes Tejedor ◽  
Francisco Sánchez-Madrid
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
T Cell Activation ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Cell Subset ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Ifn Γ

Cell adhesion molecules have a key role in the migration of T cells to inflammatory foci. However, the effect of the endothelial-lymphocyte interaction on the activation of the latter cells remains unresolved. We have studied the effect of resting and stimulated endothelial cells (ECs) on the activation of peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25 activation antigens. The incubation of PBTLs with tumor necrosis factor-–activated EC monolayers, either alive or fixed, induced the expression of CD69 but not CD25, preferentially in the CD8+CD45RO+ cell subset. Furthermore, it induced the production of cytokines such as IFN-γ, but not that of interleukin-2 (IL-2) and IL-4. EC treated with other stimuli such as IL-1β, IFN-γ, or lipopolysaccharide also showed the same proactivatory effect on T cells. Lymphocyte activation was almost completely inhibited by blocking anti-CD18 and anti–intercellular adhesion molecule-1 (anti–ICAM-1) monoclonal antibodies (MoAbs), but only slightly affected by MoAbs against CD49d, vascular cell adhesion molecule-1, and anti–IL-15. In addition, the interaction of PBTL with immobilized ICAM-1 induced CD69 expression in the same memory T-cell subset. IL-15 induced T-cell activation with expression of CD69 and CD25, and production of IFN-γ, and its effect was additive with that triggered by cell adhesion to either EC or immobilized ICAM-1. The transmigration of PBTLs through either confluent EC monolayers or ICAM-1–coated membranes also induced efficiently the expression of CD69. When IL-15 was used as chemoattractant in these assays, a further enhancement in CD69 expression was observed in migrated cells. Together these results indicate that stimulated endothelium may have an important role in T-cell activation, through the lymphocyte function antigen-1/ICAM-1 pathway, and that IL-15 efficiently cooperates in this phenomenon. These observations could account for the abundance of CD69+ cells in the lymphocytic infiltrates of several chronic inflammatory diseases.

scholarly journals Structure, Expression, and Function of ICAM-5

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Heping Yang
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Synapse Formation ◽  
The Other ◽  
Intercellular Adhesion Molecule ◽  
Cellular Functions ◽  
Binding Partners ◽  
The Central Nervous System ◽  
And Function

Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin, TLN) is a member of the ICAM family of adhesion proteins. As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ICAM subgroup; however, ICAM-5 has several unique properties compared to the other ICAMs. With its nine extracellular Ig domains, ICAM-5 is the largest member of ICAM subgroup identified so far. Therefore, it is much more complex than the other ICAMs. The expression of ICAM-5 is confined to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in the immune and blood systems. The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the telencephalon. As a somatodendrite-specific adhesion molecule, ICAM-5 not only participates in immune-nervous system interactions, it could also participate in neuronal activity, Dendrites’ targeting signals, and cognition. It would not be surprising if future investigations reveal more binding partners and other related functions of ICAM-5.

scholarly journals Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium.

1993 ◽  
Vol 177 (1) ◽  
pp. 185-190 ◽  
Author(s):  
Y van Kooyk ◽  
E van de Wiel-van Kemenade ◽  
P Weder ◽  
R J Huijbens ◽  
C G Figdor
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
T Lymphocytes ◽  
Adhesion Molecule ◽  
Leukemia Cell ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Activated T Cells ◽  
Late Antigen

Lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1)-and very late antigen 4/vascular cell adhesion molecule 1 (VLA-4/VCAM-1)-mediated adhesion of T lymphocytes to endothelial cells (EC) can be regulated by increased expression of ICAM-1 and VCAM-1 upon cytokine treatment of EC, or by activation of the integrin molecules LFA-1 and VLA-4 on T cells. Here, we provide evidence that preferential usage of LFA-1 over VLA-4 is yet another mechanism to control T cell adhesion. We observed that binding of activated T lymphocytes, as opposed to resting T cells, to EC is essentially mediated through LFA-1 and not through VLA-4. VLA-4-mediated adhesion of T cells to EC is only found when LFA-1 is not expressed or not functional, as observed for several T cell leukemia cell lines. These results suggest that LFA-1-mediated adhesion dominates and may downregulate VLA-4-mediated adhesion through an unidentified mechanism.

scholarly journals Dual Role of H-Ras in Regulation of Lymphocyte Function Antigen-1 Activity by Stromal Cell-derived Factor-1α: Implications for Leukocyte Transmigration

2001 ◽  
Vol 12 (10) ◽  
pp. 3074-3086 ◽  
Author(s):  
Kim S.C. Weber ◽  
Georg Ostermann ◽  
Alma Zernecke ◽  
Andreas Schröder ◽  
Lloyd B. Klickstein ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Stromal Cell ◽  
Jurkat Cells ◽  
Mitogen Activated Protein Kinase ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Stromal Cell Derived Factor

We investigated the role of H-Ras in chemokine-induced integrin regulation in leukocytes. Stimulation of Jurkat T cells with the CXC chemokine stromal cell-derived factor-1α (SDF-1α) resulted in a rapid increase in the phosphorylation, i.e., activation of extracellular signal receptor-activated kinase (ERK) but not c-Jun NH2-terminal kinase or p38 kinase, and phosphorylation of Akt, reflecting phosphatidylinositol 3-kinase (PI3-K) activation. Phosphorylation of ERK in Jurkat cells was enhanced and attenuated by expression of dominant active (D12) or inactive (N17) forms of H-Ras, respectively, while N17 H-Ras abrogated SDF-1α-induced Akt phosphorylation. SDF-1α triggered a transient regulation of adhesion to intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 mediated by lymphocyte function antigen-1 (LFA-1) and very late antigen-4 (VLA-4), respectively, and a rapid increase in LFA-1 binding to soluble ICAM-1.Ig, which was inhibited by D12 but not N17 H-Ras. Both D12 and N17 H-Ras abrogated the regulation of LFA-1 but not VLA-4 avidity, and impaired LFA-1–mediated transendothelial chemotaxis but not VLA-4–dependent transmigration induced by SDF-1α. Analysis of the mutant Jurkat J19 clone revealed LFA-1 with constitutively high affinity and reduced ERK phosphorylation, which were partially restored by expression of active H-Ras. Inhibition of PI3-K blocked the up-regulation of Jurkat cell adhesion to ICAM-1 by SDF-1α, whereas inhibition of mitogen-activated protein kinase kinase impaired the subsequent down-regulation and blocking both pathways abrogated LFA-1 regulation. Our data suggest that inhibition of initial PI3-K activation by inactive H-Ras or sustained activation of an inhibitory ERK pathway by active H-Ras prevail to abolish LFA-1 regulation and transendothelial migration induced by SDF-1α in leukocytes, establishing a complex and bimodal involvement of H-Ras.

scholarly journals Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate

2017 ◽  
Vol 4 (6) ◽  
pp. e401 ◽  
Author(s):  
Amandine Mathias ◽  
Sylvain Perriot ◽  
Mathieu Canales ◽  
Claudia Blatti ◽  
Coline Gaubicher ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Opportunistic Infections ◽  
Dimethyl Fumarate ◽  
Intercellular Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Objective:To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile.Methods:We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36–48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4+ and CD8+ T cells. The adhesion profiles of CD3+ T cells to specific integrin ligands (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and mucosal vascular addressin cell adhesion molecule-1 [MAdCAM-1]) were measured in vitro before and after 12 and 36–48 months.Results:NTZ decreased the frequency of α4β1+ and α4β7+ integrin expressing T cells and the binding of these cells to VCAM-1 and MAdCAM-1, respectively. After 12 months, DMF induced a decreased frequency of αLhighCD4+ T cells combined with reduced binding to ICAM-1. By contrast, with FTY, there was a doubling of the frequency of α4β1+ and αLhigh, but a decreased frequency of α4β7+ T cells. Strikingly, the binding of α4β1+, α4β7+, and to a lesser extent of αLhigh T cells to VCAM-1, MAdCAM-1, and ICAM-1, respectively, was decreased at month 12 under FTY treatment. The presence of manganese partially restored the binding of these T cells to VCAM-1 in vitro, suggesting that FTY interferes with integrin activation.Conclusions:In addition to NTZ, DMF and FTY but not other tested DMTs may also decrease T-cell–mediated immune surveillance of the CNS. Whether this mechanism may contribute to the onset of CNS opportunistic infections remains to be shown.

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