scholarly journals Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient. Inhibition by suppressor T cells.

1983 ◽  
Vol 157 (5) ◽  
pp. 1448-1460 ◽  
Author(s):  
C D Mills ◽  
R J North
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Cell Response ◽  
Passive Transfer ◽  
T Cell Response ◽  
Suppressor T Cells ◽  
Tumor Bearing ◽  
Draining Lymph Node ◽  
Adoptive Immunity

The results of this study with the P815 mastocytoma confirm the results of previous studies that showed that the passive transfer of tumor-sensitized T cells from immunized donors can cause the regression of tumors growing in T cell-deficient (TXB) recipients, but not in normal recipients. The key additional finding was that the expression of adoptive immunity against tumors growing in TXB recipients is immediately preceded by a substantial production of cytolytic T cells in the recipients' draining lymph node. On the other hand, failure of adoptive immunity to be expressed against tumors growing in normal recipients was associated with a cytolytic T cell response of much lower magnitude, and a similar low magnitude response was generated in TXB recipients infused with normal spleen cells and in tumor-bearing control mice. Because the passively transferred sensitized T cells possessed no cytolytic activity of their own, the results indicate that the 6-8-d delay before adoptive immunity is expressed represents the time needed for passively transferred helper or memory T cells to give rise to a cytolytic T cell response of sufficient magnitude to destroy the recipient's tumor. In support of this interpretation was the additional finding that inhibition of the expression of adoptive immunity by the passive transfer of suppressor T cells from tumor-bearing donors was associated with a substantially reduced cytolytic T cell response in the recipient's draining lymph node. The results serve to illustrate that interpretation of the results of adoptive immunization experiments requires a knowledge of the events that take place in the adoptively immunized recipient. They support the interpretation that suppressor T cells function in this model to "down-regulate" the production of cytolytic effector T cells.

scholarly journals Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire

2021 ◽  
Vol 17 (6) ◽  
pp. e1009602
Author(s):  
Ivy K. Brown ◽  
Nathan Dyjack ◽  
Mindy M. Miller ◽  
Harsha Krovi ◽  
Cydney Rios ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Cell Response ◽  
Helminth Infection ◽  
T Cell Response ◽  
Specific Gene ◽  
Nippostrongylus Brasiliensis ◽  
Tissue Specific ◽  
Antigen Reactivity

The CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4+ T cell response. While the most prevalent clones and clonotypes exhibited some tissue selectivity, most were observed to reside in both the lung and lung-draining lymph nodes. Antigen-reactivity of the broader repertoires was predicted to be shared across both tissues and individual mice. Transcriptome, trajectory, and chromatin accessibility analysis of lung and lymph-node repertoires revealed three unique but related populations of responding IL-4+ CD4+ T cells consistent with T follicular helper, T helper 2, and a transitional population sharing similarity with both populations. The shared antigen reactivity of lymph node and lung repertoires combined with the adoption of tissue-specific gene programs allows for the pairing of cellular and humoral responses critical to the orchestration of anti-helminth immunity.

scholarly journals Modelling the effects of lymph node swelling on T-cell response

2020 ◽  
Author(s):  
Sarah C Johnson ◽  
Jennifer Frattolin ◽  
Lowell T. Edgar ◽  
Mohammad Jafarnejad ◽  
James E. Moore
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cell Trafficking ◽  
T Cell Trafficking ◽  
Effector T Cell ◽  
Sphingosine 1 Phosphate

AbstractSwelling of the lymph nodes is commonly observed during the adaptive immune response, yet its impacts on T cell trafficking and subsequent immune response are not well known. To better understand the effect of macro-scale alterations in the lymph node, we developed an agent-based model of the lymph node paracortex, describing T cell trafficking and response to antigen-presenting dendritic cells alongside swelling-induced changes in T cell recruitment and egress, and regulation of expression of egress-modulating T cell receptor Sphingosine-1-phosphate receptor-1. Validation of the model was achieved with in-silico replication of a range of published in-vivo and cell culture experiments. Analysis of CD4+ and CD8+ effector T cell response under varying swelling conditions showed that paracortical swelling aided initial T cell activation but could inhibit subsequent effector CD8+ T cell production if swelling occurs too early in the T cell proliferative phase. A global sensitivity analysis revealed that the effects of some parameters switch from aiding to inhibiting T cell response over a ten day response period. Furthermore, temporarily extending retention of newly differentiated effector T cells, mediated by Sphingosine-1-phosphate receptor-1 expression, mitigated some of the effects of early paracortical swelling. These results suggest that targeting the timing of lymph node swelling and temporary effector T cell retention may offer new ways to manipulate immune response.Author summaryWithin the lymph nodes the interaction of T cells and antigen presenting cells play a crucial role in initiating the adaptive immune response, resulting in effector T cells that travel to the infection site. Accompanying swelling of lymph nodes is commonly observed, yet the impact on T cell trafficking through the node and the subsequent immune response are not well known. We developed a novel agent-based model of a lymph node, describing immune response-induced expansion, contraction and changes in T cell recruitment and egress. We also describe the regulation of T cell expression of the Sphingosine-1-phosphate receptor-1, which is known to play an important role in T cell trafficking. We found that although swelling aids T cell activation, too early an increase in paracortical volume hinders the CD8+ effector T cell response. We also found that temporarily maintaining the down-regulation of Sphingosine-1-phosphate receptor-1 expression on newly differentiated effector T cells greatly increased the overall effector T cell output, and could counteract the loss in effector TC production due to early swelling. Our findings suggest that targeting the timing of lymph node swelling and temporary effector T cell retention may offer new ways to manipulate immune response.

scholarly journals Development of a novelFrancisella tularensisLive Vaccine Strain expressing ovalbumin provides insight intoFrancisella tularensis-specific CD8+T cell responses

2017 ◽  
Author(s):  
David E. Place ◽  
David R. Williamson ◽  
Yevgeniy Yuzefpolskiy ◽  
Bhuvana Katkere ◽  
Surojit Sarkar ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Vaccine Strain ◽  
T Cell Responses ◽  
T Cell Response ◽  
Effective Vaccine ◽  
Cell Responses ◽  
Virulent Strains ◽  
Draining Lymph Node

ABSTRACTProgress towards a safe and effective vaccine for the prevention of tularemia has been hindered by a lack of knowledge regarding the correlates of protective adaptive immunity and a lack of tools to generate this knowledge. CD8+T cells are essential for protective immunity against virulent strains ofFrancisella tularensis, but to-date, it has not been possible to study these cells in a pathogen-specific manner. Here, we report the development of a tool for expression of the model antigen ovalbumin (OVA) inF. tularensis, which allows for the study of CD8+T cell responses to the bacterium. We demonstrate that in response to intranasal infection with theF. tularensisLive Vaccine Strain, pathogen-specific CD8+T cells expand after the first week and produce IFN-γ but not IL-17. Effector and central memory subsets develop with disparate kinetics in the lungs, draining lymph node and spleen. Notably,F. tularensis-specific cells are poorly retained in the lungs after clearance of infection. We also show that intranasal vaccination leads to more pathogen-specific CD8+T cells in the lung-draining lymph node compared to scarification vaccination, but that an intranasal booster overcomes this difference. Together, our data show that this novel tool can be used to study multiple aspects of the CD8+T cell response toF. tularensis. Use of this tool will enhance our understanding of immunity to this deadly pathogen.

scholarly journals TLR7 Modulated T Cell Response in the Mesenteric Lymph Node of Schistosoma japonicum-Infected C57BL/6 Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Jiale Qu ◽  
Xiuxue Yu ◽  
Chenxi Jin ◽  
Yuanfa Feng ◽  
Shihao Xie ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Immune Responses ◽  
Mesenteric Lymph Node ◽  
Cell Response ◽  
Early Phase ◽  
T Cell Response ◽  
Mesenteric Lymph ◽  
Tlr7 Agonist

Toll-like receptors (TLRs) play an important role in regulating immune responses during pathogen infection. However, roles of TLRs on T cells reside in the mesenteric lymph node (MLN) were not be fully elucidated in the course of S. japonicum infection. In this study, T lymphocytes from the mesenteric lymph node (MLN) of S. japonicum-infected mice were isolated and the expression and roles of TLR2, TLR3, TLR4, and TLR7 on both CD4+ and CD8+ T cells were compared. We found that the expression of TLR7 was increased in the MLN cells of S. japonicum-infected mice, particularly in CD4+ and CD8+ T cells (P<0.05). R848, a TLR7 agonist, could enhance the production of IFN-γ from MLN T cells of infected mice (P<0.05), especially in CD8+ T cells (P<0.01). In TLR7 gene knockedout (KO) mice, the S. japonicum infection caused a significant decrease (P<0.05) of the expression of CD25 and CD69, as well as the production of IFN-γ and IL-4 inducted by PMA plus ionomycin on both CD4+ and CD8+ T cells. Furthermore, the decreased level of IFN-γ and IL-4 in the supernatants of SEA- or SWA-stimulated mesenteric lymphocytes was detected (P<0.05). Our results indicated that S. japonicum infection could induce the TLR7 expression on T cells in the MLN of C57BL/6 mice, and TLR7 mediates T cell response in the early phase of infection.

scholarly journals Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda W. K. AuYeung ◽  
Robert C. Mould ◽  
Ashley A. Stegelmeier ◽  
Jacob P. van Vloten ◽  
Khalil Karimi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Response ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Cell Immunity ◽  
Vesicular Stomatitis

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.

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