Facial Nerve Transection Causes Expansion of Myelin Autoreactive T Cells in Regional Lymph Nodes and T Cell Homing to the Facial Nucleus

Autoimmunity ◽  
1992 ◽  
Vol 13 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Tomas Olsson ◽  
Per Diener ◽  
Åke Ljungdahl ◽  
Bo Höjeberg ◽  
Peter H. Van Der Meide ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Facial Nerve ◽  
Lymph Nodes ◽  
Nerve Transection ◽  
Facial Nucleus ◽  
Regional Lymph Nodes ◽  
Autoreactive T Cells ◽  
Cell Homing ◽  
T Cell Homing

scholarly journals Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jennifer D. Helble ◽  
Rodrigo J. Gonzalez ◽  
Ulrich H. von Andrian ◽  
Michael N. Starnbach
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Chlamydia Trachomatis ◽  
Genital Tract ◽  
Gamma Interferon ◽  
Cell Homing ◽  
Content Type ◽  
T Cell Homing ◽  
Ifn Γ

ABSTRACT While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.

scholarly journals Comprehensive Analysis of Chemokines in Host Organs and Their Corresponding Receptors on Donor T-Cells in Xenogeneic Gvhd Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5676-5676
Author(s):  
Yasufumi Kawasaki ◽  
Kazuya Sato ◽  
Hirofumi Nakano ◽  
Kiyomi Mashima ◽  
Daisuke Minakata ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
Research Funding ◽  
Cell Homing ◽  
Human T Cell ◽  
Human T Cells ◽  
Donor T Cells ◽  
T Cell Homing

Abstract Background After hematopoietic stem cell transplantation, donor T-cells home to secondary lymphoid organs and recognize alloantigens within MHC molecules presented by host APCs. Following activation, donor T-cells acquire effector functions and then migrate into host organs along the chemokine gradients. Animal models targeting chemokine signals for prevention or treatment of GVHD have shown promising results; however, there have been significant inconsistencies among studies probably due to differences in species and conditioning regimens. The aim of this study is to evaluate the role of chemokines and their receptors, CCR5 (receptor of CCL3-5) and CXCR3 (receptor of CXCL9-10), in human T-cell homing and the development of GVHD using xenogeneic GVHD mouse model. Methods NOG mice received 250cGy of total body irradiation (TBI) if not otherwise specified, and were subsequently injected intravenously with human pan T-cells. All mice developed severe GVHD and died within 2 weeks, while the mice that received TBI only survived without any symptoms of GVHD. Peripheral blood was collected from mice at a certain interval for chemokine measurement. To assess the expression of chemokine receptors and genes associated with T-cell homing, cells were harvested from GVHD target organs of mice at day 9. For CCR5 blockage, mice were treated with 31 mg/kg maraviroc once daily by oral gavage after transplantation. Results Extensive infiltration of human T-cells and tissue destruction were observed in lungs and liver, but less severely in colon of GVHD mice. Consistent with this, quantitative real-time PCR analysis for five chemokine-related genes detected up-regulation of murine CXCL9 and CXCL10 in lungs, CCL4 in lungs and liver, but no up-regulation in colon. Similarly, the multiplex analysis of nine chemokines in plasma showed a marked increase in murine CCL4, CXCL9, and CXCL10 in GVHD mice. These observations suggest that the increased expression of CCL4, CXCL9, and CXCL10 on individual organs and following their systemic release play a critical role in the homing of allogeneic T-cells. Quantitative real-time PCR analysis of 84 genes associated with chemokines and chemokine receptors in human T-cells obtained from GVHD target organs revealed down-regulation of 36 genes, most of which are critical for T-cell homing into lymph nodes, such as CCL21 (-6.73-fold) and its receptor, CCR7 (-51.6-fold), and up-regulation of 16 genes such as CCL3 (225.5-fold), CCL4 (25.2-fold), CCR1 (11.4-fold), CCR5 (3.94-fold), and CXCL10 (2.88-fold). Focusing on chemokine receptors on human T-cells, flow cytometric analysis showed significantly higher expression of CCR5 on CD4+ and CD8+ T-cells, and CXCR3 on CD4+ T-cells in GVHD mice, whereas CXCR3 on CD8+ T-cells was strongly expressed even in resting state. Tissue damages were less apparent in GVHD mice that received human T-cells only compared with irradiated GVHD mice. Consistent with this, not only a total number but also the proliferation rate of human T-cells was decreased in non-irradiated GVHD mice. Also, non-irradiated GVHD mice showed significantly decreased plasma CCL4 and CXCL10 levels in plasma, and lower expression of CCR5 on CD4+ and CD8+ T-cells, and CXCR3 on CD4+ T-cells. The same was observed, to a significantly greater extent, in MHC class I/II deficient mice, suggesting that recognition of host MHC molecules by T-cells are critical for both host and donor chemokine signals. Taken together, TBI promotes host chemokine secretion and chemokine receptor expression on donor T-cells, leading to faster recruitment of donor T-cells into host organs and their proliferation. Contrary to the previous reports, CCR5 inhibitor treatment failed to attenuate GVHD and to improve the survival of mice. Although none of chemokine ligands but CCL4 was up-regulated on the liver, the number of infiltrated T-cells and tissue destruction were almost equivalent compared to the control. These observations indicate that compensatory chemokine pathways involving alternative receptors for CCL3-5, such as CCR1 and CCR2 on effector T-cells may overcome CCR5 blockage. Conclusion This study firstly provides a comprehensive picture of human T-cell homing through CCR5 and CXCR3 signaling in xenogeneic GVHD models. Our data supports the development of novel preventive and therapeutic strategies targeting chemokine signaling for GVHD. Disclosures Fujiwara: Shire: Consultancy; Pfizer: Consultancy; Chugai: Consultancy; Kirin: Consultancy; Kyowa-Hakko: Consultancy; Astellas: Consultancy. Ohmine:Kyowa Hakko Kirin: Speakers Bureau; Takara Bio: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda Pharmaceutical: Speakers Bureau; Celgene Corporation: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Ono Pharmaceutical: Consultancy. Muroi:Japanese Red Cross Society: Speakers Bureau; Dickinson and Company: Speakers Bureau; Becton: Speakers Bureau; JCR: Speakers Bureau. Kanda:Taisho-Toyama: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Asahi-Kasei: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Tanabe-Mitsubishi: Research Funding; CSL Behring: Research Funding; Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; MSD: Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Taiho: Research Funding; Nippon-Shinyaku: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria.

scholarly journals γδ T Cell Homing to Skin and Migration to Skin-Draining Lymph Nodes Is CCR7 Independent

2011 ◽  
Vol 188 (2) ◽  
pp. 578-584 ◽  
Author(s):  
Manouk Vrieling ◽  
Wiebren Santema ◽  
Ildiko Van Rhijn ◽  
Victor Rutten ◽  
Ad Koets
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Γδ T Cell ◽  
Cell Homing ◽  
T Cell Homing ◽  
And Migration ◽  
Draining Lymph Nodes

scholarly journals T-cell Homing Therapy for Reducing Regulatory T Cells and Preserving Effector T-cell Function in Large Solid Tumors

2018 ◽  
Vol 24 (12) ◽  
pp. 2920-2934 ◽  
Author(s):  
Jiemiao Hu ◽  
Chuang Sun ◽  
Chantale Bernatchez ◽  
Xueqing Xia ◽  
Patrick Hwu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Solid Tumors ◽  
Cell Function ◽  
Cell Homing ◽  
Effector T Cell ◽  
T Cell Function ◽  
T Cell Homing

Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 816-825 ◽  
Author(s):  
Stéphanie Beq ◽  
Sandra Rozlan ◽  
David Gautier ◽  
Raphaëlle Parker ◽  
Véronique Mersseman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rhesus Macaques ◽  
Receptor Expression ◽  
Cell Depletion ◽  
Critical Function ◽  
T Cell Depletion ◽  
Cell Homing ◽  
T Cell Homing

AbstractInterleukin-7 (IL-7), the principal cytokine implicated in thymopoiesis and peripheral T-cell homeostasis, is presently under evaluation in human diseases characterized by persistent lymphopenia. Unexpectedly, before the eventual IL-7–driven T-cell expansion, all treated patients showed a profound T-cell depletion 24 hours after injection. The current study uses the rhesus macaque model to investigate the mechanisms involved in this IL-7–induced T-cell depletion. We identify a new critical function of IL-7 that induces massive and rapid T-cell migration from the blood into various organs, including lymph nodes, parts of the intestine, and the skin. This homing process was initiated after the induction of chemokine receptor expression by circulating T cells and the production of corresponding chemokines in target organs. Finally, we demonstrate that the IL-7–induced cell cycling is initiated within these organs before T cells migrate back into the bloodstream, indicating that T-cell homing is required for in vivo IL-7 function.

scholarly journals The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell–expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1314-1322 ◽  
Author(s):  
Cornelia Halin ◽  
M. Lucila Scimone ◽  
Roberto Bonasio ◽  
Jean-Marc Gauguet ◽  
Thorsten R. Mempel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Integrin Activation ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Sphingosine 1 Phosphate ◽  
T Cell Homing ◽  
Prolonged Retention ◽  
Lymphocyte Egress

AbstractSphingosine-1-phosphate (S1P) and its receptor S1P1 control T-cell egress from thymus and secondary lymphoid organs (SLOs). To further define the role of S1P1 in lymphocyte trafficking, we performed adoptive transfer experiments and intravital microscopy (IVM) using both S1P1–/– lymphocytes and recipient wild-type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P receptors. S1P1 deficiency and FTY720 caused rapid disappearance of T cells from blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed by multiphoton IVM. However, S1P1–/– lymphocytes displayed reduced short-term homing to PLNs due to attenuated integrin-mediated firm arrest in high endothelial venules (HEVs). By contrast, S1P1–/– T cells homed normally to Peyer patches (PPs), whereas S1P1–/– B cells had a marked defect in homing to PPs and arrested poorly in PP HEVs. Therefore, S1P1 not only controls lymphocyte egress from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin activation during homing. Interestingly, FTY720 treatment enhanced accumulation of both S1P1 sufficient and S1P1–/– T cells in PPs by enhancing integrin-mediated arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that are independent of T-cell–expressed S1P1.

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