The MOPC-21 monoclonal antibody is ideal for use as anon-reactive isotype-matched control for mouse IgG1 antibodies in mostin vivoand，andin vitroapplications。
The antibody solution should be stored at the stock concentration at4°C。Do not freeze。
*其他quality control measures for ourInVivoPlus™products include advanced binding validation，murine pathogen screening，protein aggregation screening，and ultra-low endotoxin levels.The superior quality of ourInVivoPlus™products will meet and exceed the strict demands and rigorous standards required forin vivoresearch.Learn more about theInVivoPlus™differencehere，here。
Faraco，G.，et al.（2018）。“Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17response”Nat Neurosci21（2）：240-249。PubMed
A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia，but it remains unclear how dietary salt harms the brain.We report that，in mice，excess dietary salt suppresses resting cerebral blood flow and endothelial function，leading to cognitive impairment.The effect depends on expansion of TH17cells in the small intestine，resulting in a marked increase in plasma interleukin-17（IL-17）。Circulating IL-17，原位，promotes endothelial dysfunction and cognitive impairment by the Rho kinase-dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells.The findings reval new gut-brain axis linking dietary habits to cognitive impament throget initive ne response compromising brain function via circulating IL-17.Thus，the TH17cell-IL-17pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated withTH17polarization。
Macal，M.，et al.（2018）。“Self-Renewal and Toll-like Receptor Signaling Sustain Exhausted Plasmacytoid Dendritic Cells during Chronic Viral Infection”Immunity48（4）：730-744e735。PubMed
Although characterization of T cell exhaustion has unlocked powerful immunotherapies，the mechanisms sustaining adaptations of short-lived innate cells to chronic inflammatory settings remain unknown.During murine chronic viral infection，we found that concerted events in bone marrow and spleen mediated by type I interferon（IFN-I）and Toll-like receptor7（TLR7）maintained a pool of functionally exhausted plasmacytoid dendritic cells（pDCs）。In the bone marrow，IFN-I compromised the number and the developmental capacity of pDC progenitors，which generated dysfunctional pDCs.Concurrently，exhausted pDCs in the periphery were maintained by self-renewal via IFN-I-and TLR7-induced proliferation of CD4（-subsets.）。On the other hand，pDC functional loss was mediated by TLR7，leading to compromised IFN-I production and resistance to secondary infection.These findings unveil the mechanism sustaining a self-perpetuating pool of functionally exhausted pDCs and provide a framework for deciphering long-term exhaustion of other short-lived innate cells during chronic inflammation。
Manlove，L.S.，et al.（2015）。“Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells”J Immunol。PubMed
BCR-ABL+acute lymphoblastic leukemia patients have transient responses to current therapies.However，the fusion of BCR to ABL generates a potential leukemia-specific Ag that could be a target for immunotherapy.We demonstrate that the immune system can limit BCR-ABL+leukemia progression although ultimathly is immune response fails.To address how BCR-ABL+leukemia escapes immune，we developed a peptide:MHC class II tetramer that labels endogenous BCR-ABL-specific CD4+T cells.Naive mice harbored asmall population of BCR-ABL-specific T cells that proliferated modestly upon immunization.The small number of naive BCR-ABL-specific T cells was duletive to，which depleted BCR-ABL-specific T cells.一致with this observation，we saw that BCR-ABL-specific T cells were cross-reactive with an endogenous peptide derived from ABL.Desppite this cross-reactivity，the remaining population of BCR-ABL reactive T cells proliferated upon immunization with the BCR-ABL fusion peptide and adjuvant.In response to BCR-ABL+leukemia，BCR-ABL-specific T cells proliferated and converted into regulatory T（Treg）cells，a process that was dependent on cross-reactivity with self-antigen，TGF-beta1，and MHC class II Ag presentation by leukemic cells.Treg cells were critical for leukemia progression in C57BL/6mice，as transient Treg cell ablation led to extended survival of leukemic Thus，us，BCR-ABL+leukemia actively suppresses antileukemia immune responses by converting cross-reactive leukemia-specific T cells into Treg cells。
Sell，S.，et al.（2015）。“Control of murine cytomegalovirus infection by gammadelta T cells”PLoS Pathog11（2）：e1004481。PubMed
Infections with cytomegalovirus（CMV）can cause severe disease in immunosuppressed patients and infected newborns。Innate as well as cellular and humoral adaptive immune effector functions contribute to the control of CMV in immunocompetent individuals.None of the innate or adaptive immune functions are essential for virus control，however。Expansion of gammadelta T cells has been observed during human CMV（HCMV）infection in the fetus and in transplant patients with HCMV reactivation but the protective function of gammadelta T cells under these conditions remains unclear。Here we show for murine CMV（MCMV）infections that mice that lack CD8and CD4alphabeta-T cells as well as B lymphocytes can control a MCMV infection that is lethal in RAG-1（-/-）mice lacking any T-and B-cells。gammadelta T cells，isolated from infected mice can kill MCMV infected target cellsin vitroand，importantly，provide long-term protection in infected RAG-1（-/-）mice after adoptive transfer。gammadelta T cells in MCMV infected hosts undergo a prominent and long-lasting phenotypic change most compatible with the view that the majority of the gammadelta T cell population persists in an effector/memory state even after resolution of the acute phase of the infection.A clonotypicalsed Vgamma and tobaslater stages of the infection in the organs where MCMV persists.These findings add gammadelta T cells as yet another protective component to the anti-CMV immune response.Our data provide clear evidence that gammadelta T cells can provide an effective control mechanism of acute CMV infections，particularly when conventional adaptive immune mechanism are insufficient or absent，like in transplant patient or in the developing immune system in utero.The findings have implications in the stem cell transplant setting，as antigen recognition by gammadelta T cells is not MHC-restricted and dual reactivity against CMV and tumors has been described。
Leon，B.，et al.（2014）。“FoxP3+regulatory T cells promote influenza-specific Tfh responses by controlling IL-2availability”Nat Commun5:3495。PubMed
Here，we test the role of FoxP3（+）regulatory T cells（Tregs）in controlling T follicular helper（Tfh）and germinal centre（GC）B-cell responses to influenza。In contrast to the idea that Tregs suppress T-cell responses，we find that Treg depletion severely reduces the Tfh cell response to influenza virus.Furthermore，Treg depletion prevents the accumulation of influenza-specific GCs.These effects are not due to alterations in TGFbeta availability or aprecursor-progeny relationship between Tregs and Tfh cells，but are instead mediated by increased availability of IL-2，wch hippressses the differeation and centiation of，compromises the GC B response.Thus，Tregs promote influenza-specific GC responses by preventing excessive IL-2signalling，which suppresses Tfh cell differentiation。
Beug，S.T.，et al.（2014）。“Smac mimetics and innate immune stimuli synergize to promote tumor death”Nat Biotechnol32（2）：182-190。PubMed
Smac mimetic compounds（SMC），a class of drugs that sensitize cells to apoptosis by counteracting the activity of inhibitor of apoptosis（IAP）proteins，have proven safe in phase1clinical trials in cancer patients.However，because SMCs act by enabling transduction of pro-apoptotic signals，SMC monotherapy may be efficacious only in the subset of patients whose tumors produce large quantities of death-inducing proteins such as inflammatory Thes，we reasoned that SMCs would synergize with agents that stimulate a potent yet safe“cytokine storm.”Here we show that oncolytic viruses and adjuvants such as poly（I:C）and CpG induce bystander death of cancer cells treated with SMCs that is mediated by interferon beta（IFN-beta），tumor necrosis factor alpha（TNF-alpha）and/or TNF-related apoptosis-inducing（TRAIL）。This combinatorial treatment resulted in tumor regression and extended survival in two mouse models of cancer.As these and other adjuvants have been proven safe in clinical trials，it may be worthwhile to explore their clinical efficicacy in combination with SMCs。
Although therapies targeting distinct cellular pathways（e.g.，anticytokine versus anti-B cell therapy）have been found to be an effective strategy for at least some patients with inflammatory arthritis，the mechanisms that determine which pathways promote arthritis development are poorly understood。We have used a transgenic mouse model to examine how variations in the CD4（+）T cell response to a surrogate self-peptide can affect the cellular pathways that are required for arthritis development。CD4（+）T cells that are high ly reactive with the self-peptide induce inflammatory arthritis that affects male and female mice equally。Arthritis develops by a B cell-independent mechanism，although it can be suppressed by an anti-TNF treatment，which prevented the accumulation of effector CD4（+）Th17 cells in the joints of treated mice。By contrast，arthritis develops with a significant female bias in the context of a more weakly autoreactive CD4（+）T cell response，and B cells play a prominent role in disease pathogenesis.In this setting of lower CD4（+）T cell autoreactivity，B cells promote the formation of autoreactive CD4（+）），and IL-17is required forarthritis development.These studies show that the degree of CD4（+）T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis。
Vokaer，B.，et al.（2013）。“IL-17A and IL-2-expanded regulatory T cells cooperate to inhibit Th1-mediated rejection of MHC II disparate skin grafts”PLoS One8（10）：e76040。PubMed
Several evidences suggest that regulatory T cells（Treg）promote Th17differentiation。基础设施，we tested the effect of IL-17A neutralization in a model of skin transplantation in which long-term graft survival depends on a strongin vivoTreg expansion induced by transient exogenous IL-2administration.As expected，IL-2 supplementation prevented rejection of MHC class II disparate skin allografts but，surprisingly，not in IL-17A-deficient recipients.We attested that IL-17Awas not required for IL-2-mediated Trpansion，intragraft recruitment or suppressive capacities.Instead，IL-17A prevented allograft rejection by inhibiting Th1alloreactivity independently of Tregs.Indeed，T-bet expression of naive alloreactive CD4+T cells and the subsequent Th1 immune response was significantly enhanced in IL-17A deficient mice.Our results illustrate for the first time a protective role of IL-17A in CD4+-mediated allograft rejection process。
Kerzerho，J.，et al.（2013）。“Programmed cell death ligand2regulates TH9differentiation and induction of chronic airway hyperreactivity”J Allergy Clin Immunol131（4）：1048-10571057e1041-1042。PubMed
BACKGROUND:Asthma is defined asa chronic inflammatory disease of the airways；however，the underlying physiologic and immunologic processes are not fully understood.OBJECTIVE:The aim of this study was to determine whether TH9cells developin vivoin a model of chronic airway hyperreactivity（AHR）and what factors control this development。THOD:We have developed anover chronic allergen exposure model using the clinically relevant antigen Aspergillus fumigatus to determine the time kinetics of TH9 developmentin vivo.RESULTS:TH9cells were detectable in the lungs after chronic allergen exposure。The number of TH9cells directly correlated with the severity of AHR，and anti-IL-9treatment decreased airway inflammation.Moreover，we have identified programmed cell death ligand（PD-L）2asanegative regulator of TH9cell differentiation。Lack of PD-L2was associated with significantly increased TGF-beta and IL-1alpha levels in the lungs，enhanced pulmonary TH 9differentation，and higher morbidity in the sensitized mice.CONCLUSION:Our findings suggest that PD-L2plays a pivotal role in the regulation of TH9Hrol in，Hronic，providing novel strategies for modulating adaptive immunity during chronic allergic responses。
yles，I.A.，et al.（2013）。“Signaling via the IL-20 receptor inhibits cutaneous production of IL-1beta and IL-17Ato promote infection with methicillin-resistant Staphylocococcus aureus”Nat Immunol14（8）：804-811。PubMed
Staphylococcus aureus causes most infections of human skin and soft tissue and is a major infectious cause of mortality.Host defense mechanism against S.aureus are incompletely understood.Interleukin19（IL-19），IL-20and IL-24signal through type I and type II IL-20receptors and are associated with inflammatory skin diseases such as psoriasis and atopic dermattis.We found here that those cytokines promoted cutaneous infection with S.aureus in mice by downregulating IL-1beta-and-1betays-17三通管接头human keratinocytes after exposure to S.aureus，and antibody blockade of the IL-20receptor improved outcomes in infected mice.Our findings identify an immunosuppressive role for IL-19，IL-20and IL-24during infection that could be therapeutically targeted to alter susceptibility infection。
Lamere，M.W.，et al.（2011）。“Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance”J Virol85（10）：5027-5035。PubMed
Seasonal influenza epidemics recurdue to antigenic drift of envelope glycoprotein antigens and immune evasion of circulating viruses.Additionally，antigenic shift can lead to influenza pandemics.Thus，universal vaccine that protects against multiple influenza virus strains could alleviate the continuing impact of this virus on human health.In mice，accelerated clearance of anew viral strain（cross-protection）canbe elicited by prior infection根（NP）.Both heterosubtypic immunity and NP-immune protection require antibody production。Here，we show that systemic immunization with NP readily accelerated clearance of a2009pandemic H1influenza virus isolate in an antibody-dependent manner.However，human immunization with trivalent influenza virus vaccine（TIV）only rarely and modestly boosted existing levels of。Similar results were observed in mice，although the reaction could be enhanced with adjuvants，by adjusting the stoichiometry among NP and other vaccine components，and by increasing the interval between TIV prime and boost.Importantly，mouse heterosubtypic immunity that had waned over several months could be enhanced by injecting purified anti-NP IgG or by boosting with NP protein，correlating with a long-lived increase in anti-NP antibody titers.Thus，current immunization strategies poorly induce NP-immune antibody that is nonetheless capable of contributing to long-lived cross-protection.The high conservation of NP antigen and the known longevity of antibody responses suggest that the antiviral activity of anti-NP IgG may providea crical invitiveed unt of unt vaccine。
