scholarly journals CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice

2009 ◽  
Vol 206 (11) ◽  
pp. 2497-2509 ◽  
Author(s):  
Kyrie Felio ◽  
Hanh Nguyen ◽  
Christopher C. Dascher ◽  
Hak-Jong Choi ◽  
Sha Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Small Animal ◽  
Mycobacterial Infection ◽  
Cell Receptor ◽  
Human Group ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Group 1

Group 1 CD1 (CD1a, CD1b, and CD1c)–restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)–infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1–restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1–restricted Mtb lipid–specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1–restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1–restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.

scholarly journals Thromboxane A2 acts as tonic immunoregulator by preferential disruption of low-avidity CD4+ T cell–dendritic cell interactions

2014 ◽  
Vol 211 (13) ◽  
pp. 2507-2517 ◽  
Author(s):  
Federica Moalli ◽  
Jovana Cupovic ◽  
Flavian Thelen ◽  
Pascal Halbherr ◽  
Yoshinori Fukui ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Thromboxane A2 ◽  
Cd4 T Cell ◽  
High Avidity ◽  
Cellular Interactions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Interactions between dendritic cells (DCs) and T cells control the decision between activation and tolerance induction. Thromboxane A2 (TXA2) and its receptor TP have been suggested to regulate adaptive immune responses through control of T cell–DC interactions. Here, we show that this control is achieved by selectively reducing expansion of low-avidity CD4+ T cells. During inflammation, weak tetramer-binding TP-deficient CD4+ T cells were preferentially expanded compared with TP-proficient CD4+ T cells. Using intravital imaging of cellular interactions in reactive peripheral lymph nodes (PLNs), we found that TXA2 led to disruption of low- but not high-avidity interactions between DCs and CD4+ T cells. Lack of TP correlated with higher expression of activation markers on stimulated CD4+ T cells and with augmented accumulation of follicular helper T cells (TFH), which correlated with increased low-avidity IgG responses. In sum, our data suggest that tonic suppression of weak CD4+ T cell–DC interactions by TXA2–TP signaling improves the overall quality of adaptive immune responses.

scholarly journals Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection

2021 ◽  
Author(s):  
Ellie N. Ivanova ◽  
Joseph C. Devlin ◽  
Terkild B. Buus ◽  
Akiko Koide ◽  
Amber Cornelius ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Cells ◽  
Transcriptional Profiling ◽  
Cell Receptor ◽  
Interferon Response ◽  
Effector Cells ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractBoth SARS-CoV-2 infection and vaccination elicit potent immune responses. A number of studies have described immune responses to SARS-CoV-2 infection. However, beyond antibody production, immune responses to COVID-19 vaccines remain largely uncharacterized. Here, we performed multimodal single-cell sequencing on peripheral blood of patients with acute COVID-19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by this vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of the B and T cell antigen receptor rearrangement of individual lymphocytes, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. While both infection and vaccination induced robust innate and adaptive immune responses, our analysis revealed significant qualitative differences between the two types of immune challenges. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the observed dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes in patients but not in immunized subjects. Analysis of B and T cell receptor repertoires revealed that while the majority of clonal B and T cells in COVID-19 patients were effector cells, in vaccine recipients clonally expanded cells were primarily circulating memory cells. Importantly, the divergence in immune subsets engaged, the transcriptional differences in key immune populations, and the differences in maturation of adaptive immune cells revealed by our analysis have far-ranging implications for immunity to this novel pathogen.

scholarly journals Cutaneous immunosurveillance by self-renewing dermal γδ T cells

2011 ◽  
Vol 208 (3) ◽  
pp. 505-518 ◽  
Author(s):  
Nital Sumaria ◽  
Ben Roediger ◽  
Lai Guan Ng ◽  
Jim Qin ◽  
Rachel Pinto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Γδ T Cells ◽  
Mycobacterial Infection ◽  
Cell Receptor ◽  
Dermal Cells ◽  
Draining Lymph Nodes

The presence of γδ T cell receptor (TCR)–expressing cells in the epidermis of mice, termed dendritic epidermal T cells (DETCs), is well established. Because of their strict epidermal localization, it is likely that DETCs primarily respond to epithelial stress, such as infections or the presence of transformed cells, whereas they may not participate directly in dermal immune responses. In this study, we describe a prominent population of resident dermal γδ T cells, which differ from DETCs in TCR usage, phenotype, and migratory behavior. Dermal γδ T cells are radioresistant, cycle in situ, and are partially depend on interleukin (IL)-7, but not IL-15, for their development and survival. During mycobacterial infection, dermal γδ T cells are the predominant dermal cells that produce IL-17. Absence of dermal γδ T cells is associated with decreased expansion in skin draining lymph nodes of CD4+ T cells specific for an immunodominant Mycobacterium tuberculosis epitope. Decreased CD4+ T cell expansion is related to a reduction in neutrophil recruitment to the skin and decreased BCG shuttling to draining lymph nodes. Thus, dermal γδ T cells are an important part of the resident cutaneous immunosurveillance program. Our data demonstrate functional specialization of T cells in distinct microcompartments of the skin.

scholarly journals Mast cells and γδ T cells are largely dispensable for adaptive immune responses after laser-mediated epicutaneous immunization

2019 ◽  
Author(s):  
Isabella Joubert ◽  
Daniel Kovacs ◽  
Sandra Scheiblhofer ◽  
Petra Winter ◽  
Evgeniia Korotchenko ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mast Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
List Type ◽  
Γδ T Cell ◽  
Adaptive Immune Responses ◽  
Knock Out ◽  
Adaptive Immune

AbstractBackgroundThe skin resembles an attractive target for vaccination due to its accessibility and abundance of resident immune cells. Cells like γδ T cells and mast cells (MCs) are part of the first line of defence against exogenous threats. Despite being important mediators for eliciting TH2 immune responses after epithelial stress, γδ T cell and MC function still remains to be completely understood. Here, we aimed to characterize their roles in shaping adaptive immune responses after laser-mediated epicutaneous immunization (EPI).Methodsγδ T cell knock out, MC depleted, and wildtype control mice were immunized with mannan-conjugated grass pollen allergen Phl p 5 (P5-MN) by laser-mediated EPI. After 2-3 immunizations, cytokine expression, T helper polarization, and antigen-specific IgG1/IgE levels were analysed. The local cytokine/chemokine milieu after laser microporation was determined.ResultsWhile the majority of inflammatory chemokines and cytokines induced by laser treatment was not affected by the presence of γδ T cells or MCs, RANTES, was elevated in γδ T cell knock out mice, and GROα and TSLP, were significantly decreased after MC depletion. However, absence of γδ T cells or depletion of MC had no substantial effect on adaptive humoral or cellular immune responses after laser-mediated EPI, except for slightly reduced IgG1 and effector T cell levels in MC depleted mice.Conclusionsγδ T cells did not play a pivotal role in shaping the humoral and cellular adaptive immune response after laser-mediated EPI, whereas MC depletion decreased numbers of effector T cells, indicating a potential role of MCs in the activation and maturation of T cells after EPI.HighlightsLaser microporation induces an inflammatory chemokine milieu at the site of immunizationγδ T cells and mast cells contribute to the steady-state or damage-induced cytokine milieu in the skinγδ T cells and mast cells are dispensable for adaptive immunity after laser-mediated immunization

Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling

2021 ◽  
Vol 6 (66) ◽  
Author(s):  
Puspa Thapa ◽  
Rebecca S. Guyer ◽  
Alexander Y. Yang ◽  
Christopher A. Parks ◽  
Todd M. Brusko ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
T Cell Receptor Signaling ◽  
Cell Receptor Signaling
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