scholarly journals IL-2 Receptor β-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo

2008 ◽  
Vol 181 (3) ◽  
pp. 1917-1926 ◽  
Author(s):  
Aysefa Doganci ◽  
Roman Karwot ◽  
Joachim H. Maxeiner ◽  
Petra Scholtes ◽  
Edgar Schmitt ◽  
...  
2005 ◽  
Vol 83 (5) ◽  
pp. 490-497 ◽  
Author(s):  
Nicola L Harris ◽  
John Holloway ◽  
Penny Fitzharris ◽  
Michael McDonald ◽  
Mali Camberis ◽  
...  

2019 ◽  
Vol 116 (52) ◽  
pp. 26788-26797
Author(s):  
Ester Badami ◽  
Olivier N. F. Cexus ◽  
Sonia Quaratino

Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (Teff) and T regulatory (Treg) CD4+Foxp3+cells. In vivo Teffare present in all immune organs, whereas the TPO-specific Tregare present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of Teffand the depletion of Tregvia activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.


1997 ◽  
Vol 185 (12) ◽  
pp. 2133-2141 ◽  
Author(s):  
Elizabeth Ingulli ◽  
Anna Mondino ◽  
Alexander Khoruts ◽  
Marc K. Jenkins

Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.


2016 ◽  
Vol 197 (7) ◽  
pp. 2653-2664 ◽  
Author(s):  
Nicole Schütze ◽  
Stefanie Trojandt ◽  
Stephanie Kuhn ◽  
Janina M. Tomm ◽  
Martin von Bergen ◽  
...  

2012 ◽  
Vol 189 (12) ◽  
pp. 5713-5721 ◽  
Author(s):  
Saki Kawashima ◽  
Koichi Hirose ◽  
Arifumi Iwata ◽  
Kentaro Takahashi ◽  
Ayako Ohkubo ◽  
...  

2006 ◽  
Vol 176 (11) ◽  
pp. 7062-7070 ◽  
Author(s):  
Paul J. Dunford ◽  
Niall O’Donnell ◽  
Jason P. Riley ◽  
Kacy N. Williams ◽  
Lars Karlsson ◽  
...  

2006 ◽  
Vol 203 (4) ◽  
pp. 1045-1054 ◽  
Author(s):  
Drew M. Catron ◽  
Lori K. Rusch ◽  
Jason Hataye ◽  
Andrea A. Itano ◽  
Marc K. Jenkins

We explored the relationship between the time of naive CD4+ T cell exposure to antigen in the primary immune response and the quality of the memory cells produced. Naive CD4+ T cells that migrated into the skin-draining lymph nodes after subcutaneous antigen injection accounted for about half of the antigen-specific population present at the peak of clonal expansion. These late-arriving T cells divided less and more retained the central–memory marker CD62L than the T cells that resided in the draining lymph nodes at the time of antigen injection. The fewer cell divisions were related to competition with resident T cells that expanded earlier in the response and a reduction in the number of dendritic cells displaying peptide–major histocompatibility complex (MHC) II complexes at later times after antigen injection. The progeny of late-arriving T cells possessed the phenotype of central–memory cells, and proliferated more extensively during the secondary response than the progeny of the resident T cells. The results suggest that late arrival into lymph nodes and exposure to antigen-presenting cells displaying lower numbers of peptide–MHC II complexes in the presence of competing T cells ensures that some antigen-specific CD4+ T cells divide less in the primary response and become central–memory cells.


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