Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts

2011 ◽  
Vol 24 (3) ◽  
pp. 157-163 ◽  
Author(s):  
E. Eggenhofer ◽  
J.F. Steinmann ◽  
P. Renner ◽  
P. Slowik ◽  
P. Piso ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mycophenolate Mofetil ◽  
T Cell ◽  
Cell Infiltration ◽  
Antigen Presenting Cell ◽  
T Cell Infiltration ◽  
Antigen Presenting

Bone marrow-derived clonal mesenchymal stem cells inhibit NK- and T-cell infiltration and reduce alopecia areata in mouse model

2016 ◽  
Vol 84 (1) ◽  
pp. e93-e94
Author(s):  
Ji Won Byun ◽  
Hyo Jin Kim ◽  
Kwangmin Na ◽  
Sun Uk Song ◽  
Myung Shin Jeon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Mouse Model ◽  
Alopecia Areata ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A+CD141+ cDC1 and CD14+ antigen-presenting cell recruitment

2021 ◽  
Vol 9 (3) ◽  
pp. e001962
Author(s):  
Bas D Koster ◽  
Marta López González ◽  
Mari FCM van den Hout ◽  
Annelies W Turksma ◽  
Berbel JR Sluijter ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
Peripheral Blood ◽  
Cell Infiltration ◽  
Antigen Presenting Cell ◽  
Reticular Dermis ◽  
T Cell Infiltration ◽  
Flow Cytometric ◽  
Antigen Presenting

BackgroundWe previously reported CpG-B injection at the primary tumor excision site prior to re-excision and sentinel node biopsy to result in immune activation of the sentinel lymph node (SLN), increased melanoma-specific CD8+ T cell rates in peripheral blood, and prolonged recurrence-free survival. Here, we assessed recruitment and activation of antigen-presenting cell (APC) subsets in the SLN and at the injection site in relation to T cell infiltration.MethodsRe-excision skin specimens from patients with clinical stage I-II melanoma, collected 7 days after intradermal injection of either saline (n=10) or 8 mg CpG-B (CPG7909, n=12), were examined by immunohistochemistry, quantifying immune subsets in the epidermis, papillary, and reticular dermis. Counts were related to flow cytometric data from matched SLN samples. Additional in vitro cultures and transcriptional analyses on peripheral blood mononuclear cells (PBMCs) were performed to ascertain CpG-induced APC activation and chemokine profiles.ResultsSignificant increases in CD83+, CD14+, CD68+, and CD123+ APC were observed in the reticular dermis of CpG-B-injected skin samples. Fluorescent double/triple staining revealed recruitment of both CD123+BDCA2+ plasmacytoid dendritic cells (DCs) and BDCA3/CD141+CLEC9A+ type-1 conventional DC (cDC1), of which only the cDC1 showed considerable levels of CD83 expression. Simultaneous CpG-B-induced increases in T cell infiltration were strongly correlated with both cDC1 and CD14 counts. Moreover, cDC1 and CD14+ APC rates in the reticular dermis and matched SLN suspensions were positively correlated. Flow cytometric, transcriptional, and chemokine release analyses of PBMC, on in vitro or in vivo exposure to CpG-B, indicate a role for the activation and recruitment of both cDC1 and CD14+ monocyte-derived APCs in the release of CXCL10 and subsequent T cell infiltration.ConclusionThe CpG-B-induced concerted recruitment of cDC1 and CD14+ APC to the injection site and its draining lymph nodes may allow for both the (cross-)priming of T cells and their subsequent homing to effector sites.

Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 2214-2219 ◽  
Author(s):  
Shaul Beyth ◽  
Zipora Borovsky ◽  
Dror Mevorach ◽  
Meir Liebergall ◽  
Zulma Gazit ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Human Mesenchymal Stem Cells ◽  
Cell Responses ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Antigen Presenting ◽  
Dose Dependent

AbstractInfusion of either embryonic or mesenchymal stem cells prolongs the survival of organ transplants derived from stem cell donors and prevents graft-versus-host-disease (GVHD). An in-depth mechanistic understanding of this tolerization phenomenon could lead to novel cell-based therapies for transplantation. Here we demonstrate that while human mesenchymal stem cells (hMSCs) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APCs; either monocytes or dendritic cells) to the cultures inhibits the T-cell responses. This contact- and dose-dependent inhibition is accompanied by secretion of large quantities of interleukin (IL)–10 and aberrant APC maturation, which can be partially overridden by the addition of factors that promote APC maturation (ie, lipopolysaccharide [LPS] or anti-CD40 monoclonal antibody [mAb]). Thus, our data support an immunoregulatory mechanism wherein hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory APCs with T-cell–suppressive properties. Our data may reveal a physiologic phenomenon whereby the development of a distinct APC population is regulated by the tissue's cellular microenvironment.

scholarly journals The landscape of T cell infiltration in human cancer and its association with antigen presenting gene expression

2015 ◽  
Author(s):  
Yasin Senbabaoglu ◽  
Andrew G Winer ◽  
Ron S Gejman ◽  
Ming Liu ◽  
Augustin Luna ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Immune Cell ◽  
T Cell Subsets ◽  
Cell Infiltration ◽  
Th2 Cells ◽  
Immune Infiltration ◽  
T Cell Infiltration ◽  
Mutation Burden ◽  
Antigen Presenting

Infiltrating T cells in the tumor microenvironment have crucial roles in the competing processes of pro-tumor and anti-tumor immune response. However, the infiltration level of distinct T cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery (APM) genes, remain poorly characterized across human cancers. Here, we define a novel mRNA-based T cell infiltration score (TIS) and profile infiltration levels in 19 tumor types. We find that clear cell renal cell carcinoma (ccRCC) is the highest for TIS and among the highest for the correlation between TIS and APM expression, despite a modest mutation burden. This finding is contrary to the expectation that immune infiltration and mutation burden are linked. To further characterize the immune infiltration in ccRCC, we use RNA-seq data to computationally infer the infiltration levels of 24 immune cell types in a discovery cohort of 415 ccRCC patients and validate our findings in an independent cohort of 101 ccRCC patients. We find three clusters of tumors that are primarily separated by levels of T cell infiltration and APM gene expression. In ccRCC, the levels of Th17 cells and the ratio of CD8+ T/Treg levels are associated with improved survival whereas the levels of Th2 cells and Tregs are associated with negative clinical outcome. Our analysis illustrates the utility of computational immune cell decomposition for solid tumors, and the potential of this method to guide clinical decision-making.

scholarly journals Microglia and Perivascular Macrophages Act as Antigen Presenting Cells to Promote CD8 T Cell Infiltration of the Brain

2021 ◽  
Vol 12 ◽  
Author(s):  
Emma N. Goddery ◽  
Cori E. Fain ◽  
Chloe G. Lipovsky ◽  
Katayoun Ayasoufi ◽  
Lila T. Yokanovich ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Myeloid Cells ◽  
Antigen Presenting Cells ◽  
Cd8 T Cell ◽  
Class I ◽  
Cell Infiltration ◽  
Host Protection ◽  
T Cell Infiltration ◽  
Antigen Presenting

CD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinflammation. The identity of the CNS-resident APC that presents antigen via major histocompatibility complex (MHC) class I to CD8 T cells is unknown. Herein, we characterize MHC class I expression in the naïve and virally infected brain and identify microglia and macrophages (CNS-myeloid cells) as APCs that upregulate H-2Kb and H-2Db upon infection. Conditional ablation of H-2Kb and H-2Db from CNS-myeloid cells allowed us to determine that antigen presentation via H-2Db, but not H-2Kb, was required for CNS immune infiltration during Theiler’s murine encephalomyelitis virus (TMEV) infection and drives brain atrophy as a consequence of infection. These results demonstrate that CNS-myeloid cells are key APCs mediating CD8 T cell brain infiltration.

Abstract 2700: CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche

2019 ◽  
Author(s):  
Caroline S. Jansen ◽  
Nataliya Prokhnevska ◽  
Viraj A. Master ◽  
Jennifer W. Carlisle ◽  
Mehmet A. Bilen ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Renal Tumors ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Antigen Presenting

Abstract 2700: CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche

2019 ◽  
Author(s):  
Caroline S. Jansen ◽  
Nataliya Prokhnevska ◽  
Viraj A. Master ◽  
Jennifer W. Carlisle ◽  
Mehmet A. Bilen ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Renal Tumors ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Antigen Presenting

scholarly journals Microglia and perivascular macrophages act as antigen presenting cells to promote CD8 T cell infiltration of the brain

2021 ◽  
Author(s):  
Emma N Goddery ◽  
Cori E Fain ◽  
Chloe G Lipovsky ◽  
Katayoun Ayasoufi ◽  
Lila T Yokanovich ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Myeloid Cells ◽  
Antigen Presenting Cells ◽  
Cd8 T Cell ◽  
Class I ◽  
Cell Infiltration ◽  
Host Protection ◽  
T Cell Infiltration ◽  
Antigen Presenting

CD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinflammation. The identity of the CNS-resident APC that presents antigen via major histocompatibility complex (MHC) class I to CD8 T cells is unknown. Herein, we characterize MHC class I expression in the naive and virally infected brain and identify microglia and macrophages (CNS-myeloid cells) as APCs that upregulate H-2Kb and H-2Db upon infection. Conditional ablation of H-2Kb and H-2Db from CNS-myeloid cells allowed us to determine that antigen presentation via H-2Db, but not H-2Kb, was required for CNS immune infiltration during Theiler′s murine encephalomyelitis virus (TMEV) infection and drives brain atrophy as a consequence of infection. These results demonstrate that CNS-myeloid cells are key APCs mediating CD8 T cell brain infiltration.

Sign in / Sign up

Export Citation Format

Share Document