Probing T Cell 3D Mechanosensing With Magnetically-Actuated Structures

The ability of cells to recognize and respond to the mechanical properties of their environment is of increasing importance in T cell physiology. However, initial studies in this direction focused on planar hydrogel and elastomer surfaces, presenting several challenges in interpretation including difficulties in separating mechanical stiffness from changes in chemistry needed to modulate this property. We introduce here the use of magnetic fields to change the structural rigidity of microscale elastomer pillars loaded with superparamagnetic nanoparticles, independent of substrate chemistry. This magnetic modulation of rigidity, embodied as the pillar spring constant, changed the interaction of mouse naïve CD4+ T cells from a contractile morphology to one involving deep embedding into the array. Furthermore, increasing spring constant was associated with higher IL-2 secretion, showing a functional impact on mechanosensing. The system introduced here thus separates local substrate stiffness and long-range structural rigidity, revealing new facets of T cell interaction with their environment.

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HIV-1 gp120 induces CD4 association with several molecules on the T cell surface and modulates T cell interaction with endothelium and homing

Immunology Letters ◽

10.1016/s0165-2478(97)86948-9 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 29

Author(s):

M Bragardo

Keyword(s):

T Cell ◽

Cell Surface ◽

Cell Interaction ◽

Hiv 1

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Faculty Opinions recommendation of Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1029236.374061 ◽

2006 ◽

Author(s):

Allan Zajac

Keyword(s):

T Cells ◽

T Cell ◽

Dendritic Cell ◽

Cd8 T Cells ◽

Cell Interaction ◽

Cd4 T Cell

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Faculty Opinions recommendation of T cell-dendritic cell interaction dynamics during the induction of respiratory tolerance and immunity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1498956.984054 ◽

2010 ◽

Author(s):

Jens V Stein

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Cell Interaction ◽

Interaction Dynamics

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PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition

Nature Communications ◽

10.1038/s41467-021-22965-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Kaitao Li ◽

Zhou Yuan ◽

Jintian Lyu ◽

Eunseon Ahn ◽

Simon J. Davis ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Clinical Success ◽

Clinical Intervention ◽

Cell Receptor ◽

Cell Interaction ◽

Antigen Recognition ◽

Inhibitory Function ◽

Src Homology

AbstractDespite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1’s targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR–pMHC–CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1’s potent inhibitory function and its value as a target for clinical intervention.

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Contrasting Impacts of Immunosuppressive Agents (Rapamycin, FK506, Cyclosporin A, and Dexamethasone) on Bidirectional Dendritic Cell-T Cell Interaction During Antigen Presentation

The Journal of Immunology ◽

10.4049/jimmunol.169.7.3555 ◽

2002 ◽

Vol 169 (7) ◽

pp. 3555-3564 ◽

Cited By ~ 94

Author(s):

Hiroyuki Matsue ◽

Chendong Yang ◽

Keiko Matsue ◽

Dale Edelbaum ◽

Mark Mummert ◽

...

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Cyclosporin A ◽

Antigen Presentation ◽

Immunosuppressive Agents ◽

Cell Interaction

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F.90. Macrophage T-Cell Interaction in the Absence of TNFR1

Clinical Immunology ◽

10.1016/j.clim.2006.04.130 ◽

2006 ◽

Vol 119 ◽

pp. S82-S83

Author(s):

Claudia Calder ◽

Andrew Dick ◽

Lindsay Nicholson

Keyword(s):

T Cell ◽

Cell Interaction

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Macrophage-T Cell Interaction Is Essential for the Induction of p75 Interleukin 2 (IL-2) Receptor and IL-2 Responsiveness in Human CD4+T Cells

Japanese Journal of Cancer Research ◽

10.1111/j.1349-7006.1991.tb01839.x ◽

1991 ◽

Vol 82 (3) ◽

pp. 257-261 ◽

Cited By ~ 9

Author(s):

Yoshihiko Nakamura ◽

Takashi Nishimura ◽

Yutaka Tokuda ◽

Nobumasa Kobayashi ◽

Katsuto Watanabe ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Interleukin 2 ◽

Cell Interaction

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Abstract 13287: Dendritic Cells Play a Critical Role in the Initiation of Atherosclerosis

Circulation ◽

10.1161/circ.130.suppl_2.13287 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Mengyao Jin ◽

Peng Liu

Keyword(s):

Cell Proliferation ◽

Dendritic Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Critical Role ◽

Cell Interaction ◽

Plaque Formation ◽

T Cell Proliferation ◽

Control Group

Introduction: Dendritic cells (DCs) that are known as professional antigen-presenting cells have been found to pre-locate in non-inflammatory arterial wall and increasingly accumulate during atherosclerosis progression. Previous findings suggested that residential DCs in the intima are responsible for capturing modified lipids and forming foam cells during the initiation of atherosclerosis. Hypothesis: DC accumulation and enhanced DC-T cell interaction play a critical role in the initiation of atherosclerosis. Methods: We measured plaque formation, vascular DC accumulation and antigen-specific T cell proliferation mediated by isolated aortic cells in ApoE-/- mice, as well as DTR-CD11c/ApoE-/- or DTR-CD11b/ApoE-/- mice for conditional depletion of DCs or macrophages, respectively. A brief high-fat diet for 10 days was used as a model of initial atherosclerosis. Results: In addition to increased intimal DC accumulation and plaque formation in aortic roots, 10 days of HFD induced T cell infiltration in ApoE-/- mice, compared to those without HFD as the control. Isolated aortic cells from mice with 10-day HFD showed stronger capability in inducing antigen-specific T cell proliferation, compare to the control (HFD: 3.14±0.71%; no HFD: 1.56±0.36%; p=0.022). Single diphtheria toxin (DT) injection at day 1 yielded approximately 50% decrease in intimal DC accumulation, as well as 60% attenuation in plaque formation in DTR-CD11c/ApoE-/- mice after 10-day HFD. Capability of stimulating antigen-specific T cell proliferation was also impaired in aortic cells from DC-depleted mice (DT-treated: 1.62±0.30%; PBS-treated: 3.04±0.59%; p= 0.004), along with reduction in indirect conduction of T cell activation. In contrast, no significant changes were found in plaque formation and DC accumulation in DT-injected DTR-CD11b/ApoE-/- mice after 10 days of HFD, compared to control group. Furthermore, depletion of CD11b+ macrophages in either aortas or spleens didn’t alter capability of inducing antigen-specific T cell proliferation in DT-injected mice. Conclusions: These results suggested that vascular DCs rather than macrophages play a more important role in T cell activation and initiation of atherosclerosis.

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