bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γ Production and Cytotoxicity of IL-2-Activated Murine NK Cells Are Differentially Regulated by MHC Class I Molecules
Authors: Kubota Akira , Lian Rebecca H. , Lohwasser Stefan , Salcedo Margarita , Takei Fumio 
Published: December 2022

AbstractActivation of NK cells by target cells leads to cytotoxicity as well as production of various cytokines including IFN-γ. MHC class I molecules on target cells regulate NK cytotoxicity. However, little is known about the regulation of IFN-γ production by NK cells. We examined the production of IFN-γ in individual murine NK cells stimulated with tumor cell lines by flow cytometric analysis of intracellular IFN-γ. Among several tumor lines tested, the rat basophilic leukemia line RBL-1 induced particularly high level of IFN-γ production in IL-2-activated NK cells, whereas other lines, including the prototypic NK target YAC-1, induced very low or no IFN-γ production. Transfection of murine classical MHC class I molecules into RBL-1 cells substantially inhibited IFN-γ production. This inhibition of IFN-γ production by MHC class I was independent of Ly-49 or CD94/NKG2A expression on NK cells. These results indicate that some target cells directly stimulate IL-2-activated NK cells and induce IFN-γ production, but the requirements for the induction of IFN-γ production seem different from those for NK cytotoxicity. Furthermore, similar to NK cytotoxicity, induction of IFN-γ production is inhibited by MHC class I on stimulating cells. However, the MHC class I-specific receptors inhibiting IFN-γ production are different from those for NK cytotoxicity.
Tolerance to Maternal Immunoglobulins: Resilience of the Specific T Cell Repertoire in Spite of Long-Lasting Perturbations
Authors: Faure Mathias , Calbo Sébastien , Kanellopoulos Jean , Drapier Anne-Marie , Cazenave Pierre-André , Rueff-Juy Dominique 
Published: December 2022

AbstractT cell tolerance is established and maintained through various mechanisms, the critical component being the persistence of the specific Ag. However, at the molecular level, the nature of the recovering TCR repertoire following breakdown of tolerance is unknown. We address this important question by following κ light chain constant region (Cκ)-specific CD4+ T cells of κ light chain knock-out (κ−/−) mice born to κ+/− mothers. These cells, which were in contact with maternal κ+ Igs from early ontogeny until weaning, were strongly tolerized. Tolerance was reversible and waned with the disappearance of peptide Cκ134–148 presentation in lymphoid organs, including the thymus. Whereas three specific Vβ-Jβ rearrangements emerged in the peptide Cκ134–148-specific CD4+ T cell response of all regular κ−/− mice, soon after breakdown of tolerance only one of these rearrangements was detected. The two others displayed a significant delay in reappearance and were still rare at 26 wk of age, while the control proliferative response had already recovered 3 mo earlier. At 52 wk of age, a complete recovery of the three canonical Vβ-Jβ rearrangements was observed. Thus, although profoundly perturbed for several months, the T cell repertoire returns to equilibrium, highlighting the resilient nature of this system.
Robust B Cell Immunity but Impaired T Cell Proliferation in the Absence of CD134 (OX40)
Authors: Pippig Susanne D. , Peña-Rossi Claudia , Long James , Godfrey Wayne R. , Fowell Deborah J. , Reiner Steven L. , Birkeland Marian L. , Locksley Richard M. , Barclay A. Neil , Killeen Nigel 
Published: December 2022

AbstractCD134 (OX40) is a member of the TNF receptor family that is expressed on activated T lymphocytes. T cells from mice that lack expression of CD134 made strong responses to a range of challenges, but they showed impaired proliferation in response to direct stimulation through the TCR with monoclonal anti-CD3ε Ab. CD134-deficient mice controlled infection with Leishmania major, Nippostrongylus brasiliensis, and Theiler’s murine encephalomyelitis virus, and they made overtly normal Ab responses to a variety of antigens. Thus, CD134 is not essential for many T cell responses in vivo, nor is it required for the provision of help to B cells. Nonetheless, a subtle role in the regulation of T cell reactivity is suggested by the effect of CD134 deficiency on in vitro T cell responses.
Distinct Activities of p52/NF-κB Required for Proper Secondary Lymphoid Organ Microarchitecture: Functions Enhanced by Bcl-3
Authors: Poljak Ljiljana , Carlson Louise , Cunningham Kirk , Kosco-Vilbois Marie H. , Siebenlist Ulrich 
Published: December 2022

AbstractMice rendered deficient in p52, a subunit of NF-κB, or in Bcl-3, an IκB-related regulator that associates with p52 homodimers, share defects in the microarchitecture of secondary lymphoid organs. The mutant mice are impaired in formation of B cell follicles and are unable to form proper follicular dendritic cell (FDC) networks upon antigenic challenge. The defects in formation of B cell follicles may be attributed, at least in part, to impaired production of the B lymphocyte chemoattractant (BLC) chemokine, possibly a result of defective FDCs. The p52- and Bcl-3-deficient mice exhibit additional defects within the splenic marginal zone, including reduced numbers of metallophilic macrophages, reduced deposition of the laminin-β2 chain and impaired expression of a mucosal addressin marker on sinus-lining cells. Whereas p52-deficient mice are severely defective in all of these aspects, Bcl-3-deficient mice are only partially defective. We determined that FDCs or other non-hemopoietic cells that underlie FDCs are intrinsically impaired in p52-deficient mice. Adoptive transfers of wild-type bone marrow into p52-deficient mice failed to restore FDC networks or follicles. The transfers did restore metallophilic macrophages to the marginal zone, however. Together, the results suggest that p52 carries out functions essential for a proper splenic microarchitecture in both hemopoietic and non-hemopoietic cells and that Bcl-3 is important in enhancing these essential activities of p52.
Activation and Targeting of Immunoglobulin Switch Recombination by Activities Induced by EBV Infection
Authors: Li Ming-jie , Maizels Nancy 
Published: December 2022

AbstractEBV is strongly associated with Burkitt’s lymphoma, a B cell malignancy. In certain types of Burkitt’s lymphoma, the c-myc gene has undergone translocation to the S regions associated with heavy chain switch recombination. It has not been established whether EBV infection induces recombination activities, which in turn promote translocation of c-myc, or whether translocation precedes viral infection and provides a growth advantage that is further enhanced by factors encoded or induced by the virus. To distinguish between these possibilities, we have compared the level of switch recombination activities in the EBV-negative lymphoma, BJAB, and in its EBV-infected derivative, BJAB-B1, in experiments that assayed recombination of an extrachromosomal switch substrate during transient transfection. We have found that BJAB-B1 and other EBV-positive B cell lines supported high levels of recombination of switch substrates, to produce junctions like those found in products of chromosomal switch recombination. In contrast, BJAB did not support comparable levels of switch substrate recombination. In EBV-positive B cell lines, the ability to support switch substrate recombination correlated with levels of LR1, a B cell-specific factor which is a transcriptional regulator of c-myc and which also appears to function in switch recombination. Our observations support the hypothesis that EBV infection can induce activities that affect switch recombination and thus contribute to the translocations of c-myc to the S regions that characterize certain classes of lymphomas.
Kupffer Cells fromSchistosoma mansoni-Infected Mice Participate in the Prompt Type 2 Differentiation of Hepatic T Cells in Response to Worm Antigens
Authors: Hayashi Nobuki , Matsui Kiyoshi , Tsutsui Hiroko , Osada Yoshio , Mohamed Raafat T. , Nakano Hiroki , Kashiwamura Shin-ichiro , Hyodo Yasuko , Takeda Kiyoshi , Akira Shizuo , Hada Toshikazu , Higashino Kazuya , Kojima Somei , Nakanishi3 Kenji 
Published: December 2022

AbstractInfection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-γ than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-γ in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.
NF-κB/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation
Authors: Donovan Carolyn E. , Mark David A. , He Hong Zhen , Liou Hsiou-Chi , Kobzik Lester , Wang Yunsheng , De Sanctis George T. , Perkins David L. , Finn Patricia W. 
Published: December 2022

AbstractThe NF-κB/Rel family of transcription factors induces many genes involved in immune and inflammatory responses. Mice with germline deletions of individual NF-κB/Rel subunits have different phenotypes, suggesting that the NF-κB/Rel transcription factors have different functions. We tested whether c-Rel promotes allergic asthma using a murine model of allergen-induced pulmonary inflammation and airway hyperresponsiveness. Our investigation focused on c-Rel, which is expressed in lymphoid cells and is important for lymphocyte activation. In response to allergen sensitization and challenge, c-Rel-deficient mice did not develop increases in pulmonary inflammation, bronchoalveolar lavage fluid eosinophilia, or total serum IgE. c-Rel deficiency also prevented the induction of airway hyperresponsiveness. Allergen-treated wild-type mice had increased DNA binding to an NF-κB consensus site. Chemokine expression was altered in allergen-treated c-Rel-deficient mice. Monocyte chemoattractant protein-1, which is regulated by NF-κB, was decreased in allergen-treated c-Rel-deficient mice relative to wild-type controls. The increase in NF-κB/Rel transcription factors after allergen challenge in wild-type mice and the decrease in allergen reactivity found in c-Rel-deficient mice indicate that c-Rel promotes allergic inflammation. Alteration of pulmonary chemokine expression in c-Rel-deficient mice may inhibit allergen-induced pulmonary inflammation and airway hyperresponsiveness.
The Rat and Mouse Homologues of MASP-2 and MAp19, components of the Lectin Activation Pathway of Complement
Authors: Stover Cordula M. , Thiel Steffen , Lynch Nicholas J. , Schwaeble Wilhelm J. 
Published: December 2022

AbstractRecently, we described two novel constituents of the multimolecular initiation complex of the mannan-binding lectin (MBL) pathway of complement activation, a serine protease of 76 kDa, termed MASP-2, and a MASP-2 related plasma protein of 19 kDa, termed MAp19. Upon activation of the MBL/MASPs/MAp19 complex, MASP-2 cleaves the fourth complement component C4, while the role of MAp19 within the MBL/MASP-1/MASP-2/MAp19 complex remains to be clarified. In humans, the mRNA species encoding MASP-2 (2.6 kb) and MAp19 (1.0 kb) arise by an alternative polyadenylation/splicing mechanism from a single structural MASP-2 gene. Here, we report the complete primary structures of the rat homologue of MASP-2 and of rat and mouse MAp19. We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex and demonstrate their exclusively hepatic biosynthesis. Southern blot and PCR analyses of rat genomic DNA indicate that as in humans, rat MASP-2 and MAp19 are encoded by a single structural gene.
Persistent T Cell Anergy in Human Type 1 Diabetes
Authors: Dosch H.-Michael , Cheung Roy K. , Karges Wolfram , Pietropaolo Massimo , Becker Dorothy J. 
Published: December 2022

AbstractAn anergic phenotype has been observed in nonobese diabetic (NOD) mice and some autoreactive T cells from patients with type I diabetes. To better understand this phenomenon, we measured T cell proliferative responses to 10 diabetes-associated and up to 9 control Ags/peptides in 148 new diabetic children, 51 age- and MHC (DQ)-matched siblings (sibs), 31 patients with longstanding diabetes, and 40 healthy controls. Most (78–91%) patient and sib responses to glutamate decarboxylase of 65 kDa (GAD65), islet cell cytoplasmic autoantibody (ICA) 69, diabetes-associated T cell epitopes in ICA69 (Tep69), and heat shock protein (Hsp) 60 involved anergic T cells that required exogenous IL-2 to proliferate. Responses to proinsulin, IA-2 (and tetanus toxoid) required no IL-2 and generated sufficient cytokine to rescue anergic T cell responses. Most new patients (85%) had autoreactive T cells, three quarters targeting more than half of the diabetes Ags. Only 7.8% of the sibs and none of the controls had such multiple T cell autoreactivities, which thus characterize overt disease. Multiple anergic and nonanergic T cell autoreactivities were sustained during 2 yr follow-up after onset and in patients with longstanding (3–26 yr) diabetes. Activated patient T cells survived severe IL-2 deprivation, requiring 20–100 times less IL-2 than normal T cells to escape apoptosis. Diabetic T cell anergy thus persists for decades and is Ag and host specific but not related to disease course. Rescue by IL-2 from bystander T cells and high resistance to apoptosis may contribute to this persistence. These data explain some of the difficulties in the routine detection of disease-associated T cells, and they emphasize challenges for immunotherapy and islet transplantation.
IV. The Deterioration of Isoagglutinins in Stored Bovine Serum. The Reactivation of the Agglutinins by the Addition of Normal Cow Serum
Authors: Little Ralph B. 
Published: December 2022

Discussion and Summary
In stored serum the isoagglutinins deteriorate rapidly. There is apparently no set rule for the rate of depletion for this varied with each individual serum tried. With the most powerful serum of Group I the agglutinative properties were inactivated after nine to sixteen days storage in the ice chest. After a serum had been stored only a few days the reaction generally was not equal to that with fresh sera.
When the agglutinative properties in stored sera were inactivated at refrigerator temperature these properties were again restored by the addition of fresh normal cow serum obtained from Subgroup IIIa.
From the results of the work presented on the reactivation of the agglutinins in both heated and stored sera the following explanation is offered tentatively. In a number of bloods the sera fail to agglutinate at different periods. Therefore, in these sera component A (thermostable substance present in heated sera) under natural conditions is depleted or altered. If concentration of component A had been unchanged, such sera should have agglutinated regularly. However, in such sera the heat labile substance is present in normal concentration for the blood always reactivates. The blood withdrawn from Group I shows that the serum component B is labile. After a serum has been heated at 60°C. for one hour or stored in the ice chest for varied periods agglutination can not be demonstrated. When mixed with an equal quantity of normal serum of Subgroup IIIa such sera again strongly agglutinate. Component A, on the other hand, under these same conditions is stable fora serum stored fourteen months in the refrigerator strongly agglutinated when an equal quantity of fresh Subgroup IIIa sera containing substance B was added.
On the Natural Immunity to Scarlet Fever of the Japanese and Chinese Residing in South Manchuria
Authors: Ando K. , Nishimura H. , Ozaki K. 
Published: December 2022

Abstract
Southern Manchuria, where the Chinese, as the native race and the Japanese, as immigrants, live under the same environment affords an appropriate field to study racial differences of natural immunity.
Experienced physicians here believe that the morbidity in scarlet fever of the Japanese is far greater than that of the Chinese. According to the investigation of antiscarlatinal committee of the Kwantung Government the morbidity of the Japanese residents is 3.06 per cent while that of the Chinese is only 0.12 per cent. These figures were obtained by dividing the number of scarlet fever cases occurring between 1921 and 1925 and treated by hospital and civil physicians attached to the S. M. R. Company by the number of the population living during the same period within the area under the jurisdiction of the Local Affairs Department of the S. M. R. Company. While these figures generally seem to be correct, the fact that there are some scarlet fever cases among the Chinese failing to make returns, should be taken into consideration.
Mechanisms of induction of paralysed dendritic cells with poor antigen presentation function following systemic inflammatory response syndrome (APP3P.103)
Authors: Villadangos Jose 
Published: December 2022

Abstract
Severe infections, trauma, burns or hemorrhage trigger SIRS, which is characterized by the release of immune-activating cytokines but is followed by weeks-long immunosuppression. Opportunistic infections post-SIRS are the main cause of mortality and morbidity in critical care patients. Immunosuppression post-SIRS may also contribute to poor vaccination outcomes in areas with high incidence of infection with malaria or other pathogens. We are characterizing the contribution of Dendritic Cell (DC) functional impairment (paralysis) to immunosuppresion in mice where SIRS is triggered by TLR ligands or by infection with viruses, bacteria or the malaria parasite. We show that SIRS changes the local environment where DC undergo final differentiation, leading to weeks-long formation of paralyzed DC with poor antigen presentation function. We have (i) characterized the mechanisms responsible for this defect; (ii) identified a unique genetic program induced in paralyzed DC; (iii) devised strategies to overcome the impaired antigen presenting function of paralyzed DC; (iv) discovered cytokines that induce local formation of paralyzed DC; and (v) blocked these cytokines with mAb to reduce paralysis. Our studies might lead to new therapies to overcome DC paralysis and restore immunocompetence post-SIRS, preventing secondary infections and death in intensive care patients. They may also lead to improved vaccination outcomes in areas with high incidence of pathogen infection.
Double-edged sword: self-acquiring Batf3-dependent dendritic cell required for anti-tumor immunity and graft rejection (APP3P.104)
Authors: Jakubzick Claudia , Atif Shaihk , Gibbings Sophie , Nelsen Michelle , Gill Ronald , Kedl Ross , Marrack Philippa 
Published: December 2022

Abstract
One of the major obstacles for the graft acceptance of tissue and organs is the mismatch of major and minor histocompatibility (H) antigens. Minor H antigens are peptides derived from polymorphic proteins and presented by antigen-presenting cells on major histocompatibility complex (MHC) molecules. Here we hypothesized that the self-acquiring, cross-presenting Batf3-dependent dendritic cell (DC) is responsible for minor-antigen graft rejection. Using three models of minor-antigen graft rejection: 1) male antigen 2) non-sex complex minor antigen and 3) skin organ transplant, we demonstrate that Batf3-dependent DCs are responsible for minor-antigen graft rejection. However, in the presence of a TLR7 ligand, the requirement for Batf3-dependent DCs is bypassed by shifting the functionality of Batf3-independent DCs to elicit minor-antigen graft rejection. Overall our study identifies the DC subtype responsible for minor-antigen graft rejection.
Transport of microspheres from the lung to the draining lymph nodes by inflammatory monocytes. (APP3P.106)
Authors: Samilo Dane , Xiong Huizhong , Carter Rebecca , Leiner Ingrid , Pamer Eric 
Published: December 2022

Abstract
Inflammatory monocytes (Ly6Chi CCR2hi) play a critical role in steering the course of responses against microbial infections of the lung. Lung monocytes can take up live fungi or bacteria and transport them to draining mediastinal lymph nodes (mLN). How microbes are taken up and trafficked by monocytes from the pulmonary site of infection is poorly understood. To study monocyte-mediated microbial trafficking, we developed a system to trace monocytes that carry particles from the lung to mLNs. Herein, we used mice expressing GFP or the diphtheria toxin receptor under the control of the CCR2 promoter to determine the impact of intratracheally instilled toll-like receptor (TLR) agonists on trafficking of with fluorescent, polystyrene microspheres from the lung to mLNs. This system recapitulates monocyte recruitment and trafficking seen during in vivo infections. Monocytes infiltrated the interstitial space in response to TLR2 agonists. And while neutrophils were the primary cell population associated with instilled microspheres in the lung, they did not deliver them independently to mLNs. Conversely, adoptively transferred monocytes successfully delivered microspheres to mLNs of CCR2+-cell-depleted mice. Our current system and findings empower us to further dissect the process of monocyte uptake of inhaled particles and antigen delivery to lymphocytes of mLNs, which may in turn inform novel vaccine strategies in an age of increasing emergence of antibiotic-resistant pathogens.
FasL-expressing B cells are major players in type 1 diabetes (BA6P.129)
Authors: Saxena Ankit , Xiao Zuoxiang , Yagita Hideo , Larman Ben , Donner Thomas , Hamad Abdel Rahim 
Published: December 2022

Abstract
B cells serve both pathogenic and regulatory roles in Type 1 diabetes (T1D). Whereas the regulatory role is mainly limited to IL-10-producing (IL-10pos) B cells, little is known about the characteristics of pathogenic B cells. Here we identified a novel population of FasLhiCD5+ B cells that is significantly increased in T1D as compared to non-diabetic autoantibody positive (Ab+) subjects. Both the FasLhi and IL-10pos sets are localized within the CD5+ B subpopulation. However, FasLhiCD5+ B cells were significantly expanded and IL-10posCD5+ B cells decreased in T1D as compared to Ab+ subjects. FasLhiCD5+ B cells do not produce IL-10 and are largely spared from activation-induced apoptosis, whereas IL-10posCD5+ B cells are prone to Fas-mediated apoptosis. Causally, using NOD mouse model, we identified FasL-expressing B cells as negative regulators of IL-10pos B cells and facilitators of islet infiltration by diabetogenic T cells. These results identify FasLhiCD5+ B cells as an elevated subpopulation in T1D subjects and initiator of the diabetogenic process in NOD mice.