A new role for interleukin‐7 in the induction of LFA‐1 and VLA‐4 adhesion molecules in Phorbol 12myristate 13acetate activated CD4+CD23+ T‐cell subset

Fratazzi, Candida; Carini, Claudio

doi:10.1111/j.1365-2222.1997.tb01180.x

Cited by 2 publications

(1 citation statement)

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“…We confirmed by confocal microscopy that IL-7 priming induced an increase in the membrane clustering of activated LFA-1 induced by CD3 cross-linking. Whilst the involvement of LFA-1 in TCR activation, and IL-7 altering adhesion via LFA-1 are not new concepts [ 16 , 44 ] the use of the SPPLAT methodology enabled us to demonstrate this mechanism of IL-7 priming of LFA-1 activation occurs in cells within 10 min of TCR activation.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation

Queiroz

Piper

Rees

et al. 2022

Biochemical Journal

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The ability of the cellular immune system to discriminate self from foreign antigens depends on the appropriate calibration of the T-cell receptor (TCR) signalling threshold. The lymphocyte homeostatic cytokine interleukin 7 (IL-7) is known to affect TCR thresholding, but the molecular mechanism is not fully elucidated. A better understanding of this process is highly relevant in the context of autoimmune disease therapy and cancer immunotherapy. We sought to characterise the early signalling events attributable to IL-7 priming; in particular, the altered phosphorylation of signal transduction proteins and their molecular localisation to the TCR. By integrating high-resolution proximity- phospho-proteomic and imaging approaches using primary T cells, rather than engineered cell lines or an in vitro expanded T cell population, we uncovered transduction events previously not linked to IL-7. We show that IL-7 leads to dephosphorylation of cytohesin interacting protein (CYTIP) at a hitherto undescribed phosphorylation site (pThr280) and alters the co-localisation of cytohesin 1 with the TCR and LFA-1 integrin. These results show that IL-7, acting via CYTIP and cytohesin-1, may impact TCR activation thresholds by enhancing the co-clustering of TCR and LFA-1 integrin.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation

Queiroz

Piper

Rees

et al. 2022

Biochemical Journal

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Homeostatic expansion of CD4+ T cells upregulates VLA-4 and exacerbates HSV-induced corneal immunopathology

Suvas

Kim

Rouse

2008

Microbes and Infection

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Using a viral induced immunopathology model, we showed that when CD4 + T cells were allowed to undergo homeostatic expansion prior to ocular HSV infection, mice developed more severe inflammatory lesions with the increased severity associated with enhanced effector function of ocular CD4 + T cells and blocking their functional activity reduced the lesion severity. Additionally, homeostatically expanded CD4 + T cells upregulated VLA-4, and in vivo administration of anti-VLA-4 mAb significantly decreased the homeostatic proliferation. Furthermore, blocking of VLA-4 interaction also diminished the infiltration of CD4 + T cells into the cornea and decreased lesion severity. Our results imply that homeostatic expansion of T cells, as could occur in a virus induced lymphopenia, may generate cells with enhanced effector function that can contribute to tissue damage. Keywords Inflammation; viral; T lymphocytes; adhesion moleculesIn healthy animals, the peripheral lymphocyte pool size remains quite constant. Conditions of lymphopenia usually induce lymphocytes to proliferate so as to restore the pool size [1]. This event, refereed to as homeostatic proliferation, involves naïve and memory lymphocytes and various factors such as self peptide reactivity [2,3], clonal competition [4,5] and different cytokines regulate their cell division [6][7][8] These homeostatically dividing cells express many activation markers characteristic of memory cells and are functionally active [9,10]. Recently, it has been argued that lymphopenia may result in the homeostatic expansion of autoreactive T cells that mediate some autoimmune diseases [11,12]. In addition, T cell homeostatic expansion (HE) may also result in the enhanced anti-tumor activity of CD8 + T cells [13]. Several viral infections induce a temporary or long term lymphopenia [14][15][16][17][18][19]. It is not clear what role, if any, the vigorous compensatory lymphocyte expansion that may follow plays in anti-viral immunity and pathology. Certain reports claim that these events may explain the association of some viruses with autoimmunity [12]. However, autoimmune disease expression *Correspondence should be addressed to: Barry T Rouse, Department of Microbiology, M409, Walters Life Sciences building, University of Tennessee, , E-mail: btr@utk.edu or suvas@oakland.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Materials and Methods Mice and virusFemale 6 to 8-wk-old BALB/c SCID (H-2 d ), mice were purchased from Harlan SpragueDawley (Indianapolis, IN) and DO11.10 (OVA-TCR Tg mice), DO11.10 IFN-γ −/− mic...

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A new role for interleukin‐7 in the induction of LFA‐1 and VLA‐4 adhesion molecules in Phorbol ¹²myristate ¹³acetate activated CD4⁺CD23⁺ T‐cell subset

Abstract: Taken together these findings point to the likelihood that IL-7 is responsible for the observed quantitative difference in the level of adhesion molecules and may open a new role of CD23 in the immune regulation.

Cited by 2 publications

References 42 publications

Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation

Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation

Homeostatic expansion of CD4+ T cells upregulates VLA-4 and exacerbates HSV-induced corneal immunopathology

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