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

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

Vaccine ◽  
2020 ◽  
Vol 38 (5) ◽  
pp. 1015-1024
Author(s):  
Isabella A. Joubert ◽  
Daniel Kovacs ◽  
Sandra Scheiblhofer ◽  
Petra Winter ◽  
Evgeniia Korotchenko ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals Early Pregnancy Human Decidua is Enriched with Activated, Fully Differentiated and Pro-Inflammatory Gamma/Delta T Cells with Diverse TCR Repertoires

2019 ◽  
Vol 20 (3) ◽  
pp. 687 ◽  
Author(s):  
Antonia Terzieva ◽  
Violeta Dimitrova ◽  
Lyubomir Djerov ◽  
Petya Dimitrova ◽  
Silvina Zapryanova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Pregnant Women ◽  
Early Pregnancy ◽  
Γδ T Cells ◽  
Γδ T Cell ◽  
Maternal Immune System ◽  
Human Decidua ◽  
Maternal Fetal Interface

Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in tissue homeostasis and repair. The variety of functions makes γδ T cells a particularly interesting population during pregnancy. In this study, we investigated the proportion, phenotype and TCR γ and δ repertoires of γδ T cells at the maternal–fetal interface and in the blood of pregnant women using FACS, immunohistochemistry and spectratyping. We found an enrichment of activated and terminally differentiated pro-inflammatory γδ T-cell effectors with specific location in the human decidua during early pregnancy, while no significant changes in their counterparts in the blood of pregnant women were observed. Our spectratyping data revealed polyclonal CDR3 repertoires of the δ1, δ2 and δ3 chains and γ2, γ3, γ4 and γ5 chains and oligoclonal and highly restricted CDR3γ9 repertoire of γδ T cells in the decidua and blood of pregnant women. Early pregnancy induces recruitment of differentiated pro-inflammatory γδ T-cell effectors with diverse TCR repertoires at the maternal–fetal interface.

719 CD122-directed interleukin-2 complexes and αPD-L1 differentially require innate and adaptive immunity to treat local and metastatic bladder cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A761-A761
Author(s):  
Ryan Reyes ◽  
Yilun Deng ◽  
Deyi Zhang ◽  
Niannian Ji ◽  
Neelam Mukherjee ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
San Antonio ◽  
Interleukin 2 ◽  
Γδ T Cells ◽  
List Type ◽  
Γδ T Cell

BackgroundαPD-L1 bladder cancer (BC) immunotherapy is effective in <30% of cases.1 To address the large αPD-L1-unresponsive subset of patients, we tested αIL-2/IL-2 complexes (IL-2c) that block IL-2 from binding high-affinity IL-2Rα (CD25) for preferential IL-2Rβ (CD122) binding.2 Immunosuppressive regulatory T cells capture IL-2 by CD25 whereas antitumor CD8+ T, γδ T, and NK cells use CD122. We hypothesized that the tumor microenvironment, including local immune cells in primary versus metastatic BC, differentially affects immunotherapy responses and that IL-2c effects could differ from, and thus complement αPD-L1.MethodsWe used PD-L1+ mouse BC cell lines MB49 and MBT-2, for orthotopic, intravesical (i.e., in bladder) and intravenous challenge studies of local versus lung metastatic BC.ResultsαPD-L1 or IL-2c alone reduced tumor burden and extended survival in local MB49 and MBT-2. Using in vivo cell depletions, we found that γδ T cells and NK cells, but strikingly not CD8+ T cells, were necessary for IL-2c efficacy in bladder. We confirmed γδ T cell requirements for IL-2c, but not αPD-L1 efficacy in γδ T cell-null TCRδKO mice. TCRβKO conventional T cell-null mice exhibited IL-2c, but not αPD-L1 responsiveness for orthotopic BC treatment. Neither agent alone treated lung metastatic MB49 or MBT-2 but the drug combination improved survival in both tumor models. Combination treatment effects in lungs were distinct from bladder, requiring CD8+ T and NK cells, but not γδ T cells.ConclusionsBC immunotherapy effects differ by anatomic compartment and use distinct mechanisms to treat primary and metastatic BC. CD122-directed IL-2 is a promising BC immunotherapy strategy, and IL-2c is a candidate mediator through innate immune effects. αPD-L1 could improve IL-2c efficacy by engagement of adaptive immune responses including to improve metastatic disease treatment efficacy.Ethics ApprovalAll procedures involving animals in this study were approved by the UT Health San Antonio Institutional Animal Care and Use Committee (IACUC) and conducted in accordance with UT Health San Antonio Department of Laboratory Animal Resources standards.ReferencesShah AY, Gao J, Siefker-Radtke AO. Five new therapies or just one new treatment? A critical look at immune checkpoint inhibition in urothelial cancer: Future Medicine, 2017.Arenas-Ramirez N, Zou C, Popp S, et al. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Science translational medicine 2016;8(367):367ra166-367ra166.

Comparative Biology of γδ T Cells

2002 ◽  
Vol 85 (4) ◽  
pp. 347-358 ◽  
Author(s):  
Zheng W. Chen
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Comparative Biology ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Biological Features ◽  
Αβ T Cells

Accumulative evidence suggests that resident γδ T cells in epithelia are biologically distinct from systemic γδ T cells in the circulation. Murine resident γδ T cells have innate immune characteristics and play an important role in tissue homeostasis after damages. In contrast, a unique subset of circulating γδ T cells in primates, like αβ T cells, can mount adaptive immune responses in infections. This article compares biological features between resident and circulating γδ T cells.

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.

Coexpression of αβ and γδ TCRs bridges innate and adaptive immunity

2020 ◽  
Vol 12 (546) ◽  
pp. eabc8941
Author(s):  
Gerald P. Morris
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Γδ T Cells ◽  
Adaptive Immune Responses ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune

T cells coexpressing αβ and γδ TCRs demonstrate characteristics of both αβ and γδ T cells, providing a link between innate and adaptive immune responses.

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 Gamma delta T cells recognize haptens and mount a hapten-specific response

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Xun Zeng ◽  
Christina Meyer ◽  
Jun Huang ◽  
Evan W Newell ◽  
Brian A Kidd ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Small Molecules ◽  
Γδ T Cells ◽  
Specific Response ◽  
Γδ T Cell ◽  
Chemical Modifications ◽  
Adaptive Immune

The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system, which until now was thought to be mediated mainly by B cell antigen receptors. Here we report that small molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, and 4-hydroxy-3-nitrophenylacetyl (NP), one of the most noted haptens, are γδ T cell antigens, recognized directly by specific γδ TCRs. Immunization with Cy3 conjugates induces a rapid Cy3-specific γδ T cell IL-17 response. These results expand the role of small molecules and chemical modifications in immunity and underscore the role of γδ T cells as unique adaptive immune cells that couple B cell-like antigen recognition capability with T cell effector function.

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