Journal of immunology最新文献_第9页

Burn injury-induced G-CSF secretion reduces spic+ erythroblastic island macrophages in the bone marrow and impairs medullary erythropoiesis. 烧伤诱导的G-CSF分泌减少骨髓中spic+红母细胞岛巨噬细胞，损害髓质红细胞生成。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-02-01 DOI: 10.1093/jimmun/vkae018

John G Noel, Holly Goetzman, Satarupa Sengupta, Mario Medvedovic, Katie G Seu, Jason C Gardner

{"title":"Burn injury-induced G-CSF secretion reduces spic+ erythroblastic island macrophages in the bone marrow and impairs medullary erythropoiesis.","authors":"John G Noel, Holly Goetzman, Satarupa Sengupta, Mario Medvedovic, Katie G Seu, Jason C Gardner","doi":"10.1093/jimmun/vkae018","DOIUrl":"10.1093/jimmun/vkae018","url":null,"abstract":"The erythroblastic island (EBI) functions as a niche in which erythroblastic island macrophages (EBIMφs) are positioned within rings of erythroblasts, providing support and signals that orchestrate efficient erythropoiesis. We postulated burn injury impacts the EBI niche, given the nearly universal presence of anemia and inflammation in burn patients, and a divergent myeloid transcriptional signature that we observed in murine bone marrow following burn injury, in which granulocyte colony-stimulating factor (G-CSF) secretion broadly attenuated the expression of EBIMφ marker genes. Notably, we identified the heme-induced transcription factor Spi-C as a robust marker of EBIMφs in Spicigfp/igfp mice. Two bone marrow cell populations, macrophages and Gr1-low monocytes, possessed cell-intrinsic Spic-GFP. Spic+ macrophages were distinguished by higher levels of green fluorescent protein, autofluorescence, F4/80, and CD163 while CD115 staining was negligible compared with Gr1-low monocytes. Application of Spicigfp/igfp mice in studies revealed a G-CSF-dependent reduction of Spic+ macrophages in postburn marrow, which coincided with a loss of erythroid cells and that G-CSF administration was sufficient to reduce Spic+ macrophages in the marrow. These results provide the first evidence that burn injuries impact the EBI niche through G-CSF-dependent reduction of Spic+ EBIMφs and support the use of Spicigfp/igfp mice in investigation of EBIMφs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 2","pages":"290-303"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization and comparison of immunity against MPXV for individuals infected with MPXV or vaccinated with modified vaccinia Ankara vaccines. MPXV感染者和改良安卡拉牛痘疫苗接种者对MPXV的免疫特性和比较

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-02-01 DOI: 10.1093/jimmun/vkae031

Aurélie Wiedemann, Mathieu Surénaud, Mathieu Hubert, José-Luis Lopez Zaragoza, Alexandre Ribeiro, Cécile Rodrigues, Emile Foucat, Harouna Diombera, Corinne Krief, Olivier Schwartz, Jean-Daniel Lelièvre, Yves Lévy

{"title":"Characterization and comparison of immunity against MPXV for individuals infected with MPXV or vaccinated with modified vaccinia Ankara vaccines.","authors":"Aurélie Wiedemann, Mathieu Surénaud, Mathieu Hubert, José-Luis Lopez Zaragoza, Alexandre Ribeiro, Cécile Rodrigues, Emile Foucat, Harouna Diombera, Corinne Krief, Olivier Schwartz, Jean-Daniel Lelièvre, Yves Lévy","doi":"10.1093/jimmun/vkae031","DOIUrl":"https://doi.org/10.1093/jimmun/vkae031","url":null,"abstract":"The 2022 Mpox virus (MPXV) outbreak revitalized questions about immunity against MPXV and vaccinia-based vaccines (VAC-V), but studies are limited. We analyzed immunity against MPXV in individuals infected with MPXV or vaccinated with the licensed modified vaccinia Ankara (MVA) Bavarian Nordic or an experimental MVA-HIVB vaccine. The frequency of neutralizing antibody responders was higher among MPXV-infected individuals than MVA vaccinees. Both MVA vaccines induced similar and strong humoral responses. Similarly, we show a higher frequency and magnitude (5-fold) of T cell responses, mainly mediated by CD8+ T cells, against a peptide pool containing selected sequences from MPXV, variola, and VAC-V in MPXV-infected individuals than MVA vaccinees. We describe a hierarchy of cross-reactive T cell responses against 5 peptide pools that are highly homologous between VAC-V and MPXV 2022, with the highest frequency of responders against MVA-121L and MVA-018L proteins. Both vaccines stimulated a notable frequency of polyfunctional CD4+ and CD8+ T cell responses, with a subset of CD4+ T cells showing a mixed cytokine profile. Finally, we found that smallpox vaccination in childhood positively affected humoral but not T cell vaccine responses, whereas these responses were not affected in people living with HIV. These findings contribute to deciphering and monitoring the profile of immunity to MPXV and MVA. In the context of a potential threat of the reemergence of smallpox following bioterrorism, the diversification and availability of potent vaccines is crucial. The comparable immunogenicity of both MVA vaccines emphasizes the potential utility of MVA-HIVB as a valuable new tool for controlling MPXV outbreaks.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 2","pages":"211-222"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maternal supplementation with α-tocopherol inhibits the development of offspring food allergy, H1R signaling and ultimately anaphylaxis early in life. 母体补充α-生育酚可抑制后代食物过敏、H1R信号和最终的早期过敏反应的发展。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-02-01 DOI: 10.1093/jimmun/vkae041

Allison E Kosins, Haoran Gao, Ross L Blankenship, Lauren N Emmerson, Joel A Ochoa, Joan M Cook-Mills

{"title":"Maternal supplementation with α-tocopherol inhibits the development of offspring food allergy, H1R signaling and ultimately anaphylaxis early in life.","authors":"Allison E Kosins, Haoran Gao, Ross L Blankenship, Lauren N Emmerson, Joel A Ochoa, Joan M Cook-Mills","doi":"10.1093/jimmun/vkae041","DOIUrl":"10.1093/jimmun/vkae041","url":null,"abstract":"Food allergy has had a rapid rise in prevalence, and thus it is important to identify approaches to limit the development of food allergy early in life. Because maternal dietary supplementation with α-tocopherol (α-T), an isoform of vitamin E, during pregnancy and nursing increases neonate plasma levels of α-T and can limit neonate development of other allergies, we hypothesized that α-T can limit development of food allergy. To assess this, male mice with mutations in their skin barrier genes (FT-/- mice) were mated with wild-type females that received a diet supplemented with α-tocopherol or a control diet. Starting at postnatal day 3, these FT+/- pups were sensitized 4 to 5 times over 2.5 weeks by skin co-exposure to the food allergen peanut extract (PNE) and the environmental allergen Alternaria alternata (Alt). Control pups were exposed to saline, PNE only or Alt only. Supplementation with α-T blocked Alt+PNE sensitization (anti-PNE-specific IgE), without blocking Alt+PNE-stimulated skin IL33, Areg, OSM, CCL11, TSLP or plasma MCPT1. However, supplementation with α-T blocked mast cell activation, the increase in plasma histamine in Alt+PNE sensitized pups, histamine receptor stimulation of endothelial PKCα signaling, and ultimately oral PNE-induced anaphylaxis in Alt+PNE sensitized mice. Thus, maternal supplementation with α-tocopherol reduced development of food allergy and anaphylaxis in neonates. These results have implications for supplementation of mothers with α-tocopherol to limit development of food allergy in neonates with skin barrier mutations.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 2","pages":"199-210"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity. 抗小鼠IL-18结合蛋白抗体刺激IL-18生物活性的研究。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 Epub Date: 2025-01-28 DOI: 10.1093/jimmun/vkae022

Arnaud Huard, Sébastien Fauteux-Daniel, Jérémie Goldstein, Praxedis Martin, Matthias Jarlborg, Julie Andries, Assunta Caruso, Alejandro Díaz-Barreiro, Emiliana Rodriguez, Laurie Vaillant, Savvas N Savvides, Cem Gabay

{"title":"Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity.","authors":"Arnaud Huard, Sébastien Fauteux-Daniel, Jérémie Goldstein, Praxedis Martin, Matthias Jarlborg, Julie Andries, Assunta Caruso, Alejandro Díaz-Barreiro, Emiliana Rodriguez, Laurie Vaillant, Savvas N Savvides, Cem Gabay","doi":"10.1093/jimmun/vkae022","DOIUrl":"10.1093/jimmun/vkae022","url":null,"abstract":"Interleukin (IL)-18 is an immunoregulatory cytokine that acts as a potent inducer of T helper 1 and cytotoxic responses. IL-18 activity is regulated by its decoy receptor IL-18 binding protein (IL-18BP) which forms a high affinity complex with IL-18 to block binding of the cognate receptors. A disbalance between IL-18 and IL-18BP associated with excessive IL-18 signaling can lead to systemic inflammation. Indeed, the severity of CpG-induced macrophage activation syndrome (MAS) is exacerbated in IL-18BP KO mice. On the contrary, targeting IL-18BP can have promising effects to enhance immune responses against pathogens and cancer. We generated monoclonal rabbit anti-mouse IL-18BP antibodies labeled from 441 to 450. All antibodies, except from antibody 443, captured mIL-18BP when used in a sandwich ELISA. Using an IL-18 bioassay, we showed that antibody 441 did not interfere with the regulatory effect of mIL-18BP, whereas all other antibodies displayed different levels of antagonism. Further experiments were performed using antibody 445 endowed with potent neutralizing activity and antibody 441. Despite binding to IL-18BP with the same affinity, antibody 445, but not antibody 441, was able to release IL-18 from preformed IL-18-IL-18BP complexes. Administration of antibody 445 significantly aggravated the severity of CpG-induced MAS as compared to antibody 441. Additional experiments using naïve WT, IL-18BP KO, and IL-18 KO mice confirmed the specificity of the neutralizing effect of antibody 445 towards IL-18BP. Our studies led to the development of a monoclonal anti-IL-18BP antibody with neutralizing activity that results in the promotion of IL-18 activities.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"180-191"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Topoisomerase 1 is required for the development and function of thymus. 拓扑异构酶1是胸腺发育和功能所必需的。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 Epub Date: 2025-01-23 DOI: 10.1093/jimmun/vkae003

Amit Kumar, Pallawi Choubey, Harshdeep Kaur, Prerana Muralidhara, Kushagra Bansal

{"title":"Topoisomerase 1 is required for the development and function of thymus.","authors":"Amit Kumar, Pallawi Choubey, Harshdeep Kaur, Prerana Muralidhara, Kushagra Bansal","doi":"10.1093/jimmun/vkae003","DOIUrl":"10.1093/jimmun/vkae003","url":null,"abstract":"Thymus organogenesis is critical for proper maturation of developing T cells. In this study, we identified Topoisomerase 1 (Top1) as a novel gene involved in thymus development and function. We created a mouse line with deletion of Top1 in thymic epithelial cells (TECs) and our results demonstrate that biallelic loss of Top1 in TECs causes congenital thymic aplasia, precipitating T cell immunodeficiency. Transcriptomic analysis provides insights into the molecular mechanism of Top1 in thymus development as we identify key genes involved in thymus organogenesis as the transcriptional targets of Top1 in TECs. Analysis of peripheral immunological compartments revealed severe loss of αβ T cells complemented with a disproportionate accumulation of γδ T cells and myeloid cells upon deletion of Top1 in TECs. The residual αβ T cells in Top1 knock-out mice were effector and oligoclonal in nature highlighting their self-reactivity. These results reveal a previously unknown role of Top1 in thymus development and T cell homeostasis. We propose Top1 as a genetic target for altered thymic development and T cell lymphopenia.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"23-39"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasmacytoid dendritic cell sensing of African swine fever virus-infected macrophages results in STING-dependent robust interferon-α production. 非洲猪瘟病毒感染巨噬细胞的浆细胞样树突状细胞感知导致sting依赖性强干扰素-α产生。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 DOI: 10.1093/jimmun/vkae008

José María Sánchez-Carvajal, Aurélie Godel, Nolwen Husson, Artur Summerfield, Obdulio García-Nicolás

{"title":"Plasmacytoid dendritic cell sensing of African swine fever virus-infected macrophages results in STING-dependent robust interferon-α production.","authors":"José María Sánchez-Carvajal, Aurélie Godel, Nolwen Husson, Artur Summerfield, Obdulio García-Nicolás","doi":"10.1093/jimmun/vkae008","DOIUrl":"https://doi.org/10.1093/jimmun/vkae008","url":null,"abstract":"While several African swine fever virus (ASFV)-encoded proteins potently interfere with the cGAS-STING (cyclic GMP-AMP synthetase-stimulator of interferon genes) pathway at different levels to suppress interferon (IFN) type I production in infected macrophages, systemic IFN-α is induced during the early stages of AFSV infection in pigs. The present study elucidates a mechanism by which such responses can be triggered, at least in vitro. We demonstrate that infection of monocyte-derived macrophages (MDMs) by ASFV genotype 2 strains is highly efficient but immunologically silent with respect to IFN type I, IFN-stimulated gene induction, and tumor necrosis factor production. Additionally, ASFV does not directly activate plasmacytoid dendritic cells (pDCs). However, coculturing pDCs with ASFV-infected MDMs results in a strong pDC response characterized by high levels of IFN-α and tumor necrosis factor. IFN type I, in turn, promoted interleukin-1 receptor antagonist production by macrophages. Similar to the sensing of infected cells by other viruses, pDC activation required integrin-mediated cognate interactions with ASFV-infected MDMs to form an interferogenic synapse. Inhibitor studies indicated that the activation of pDCs requires the STING pathway and the formation of gap junctions. While IL-4-polarized macrophages showed increased susceptibility, IFN-γ-polarized ASFV-infected macrophages induced higher pDC activation. Pretreatment of pDCs with IFN-β and IFN-γ also enhanced IFN-α production in response to ASFV-infected macrophages, highlighting the influence of the immunological microenvironment. These findings suggest that the IFN-α detected during ASFV infection in pigs may be a result of pDC sensing ASFV-infected macrophages.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"130-140"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Teleost IgM+ plasma-like cells: beyond antibody secretion. 硬骨鱼IgM+浆样细胞：不能分泌抗体。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 DOI: 10.1093/jimmun/vkae001

Liting Wu, Esther Morel, Rocío Simón, Pedro Perdiguero, Yong-An Zhang, Jianmin Ye, Carolina Tafalla

{"title":"Teleost IgM+ plasma-like cells: beyond antibody secretion.","authors":"Liting Wu, Esther Morel, Rocío Simón, Pedro Perdiguero, Yong-An Zhang, Jianmin Ye, Carolina Tafalla","doi":"10.1093/jimmun/vkae001","DOIUrl":"https://doi.org/10.1093/jimmun/vkae001","url":null,"abstract":"Upon antigen encounter, B cells start a differentiation process toward antibody-secreting cells (ASCs), initially plasmablasts, and eventually long-lived plasma cells. All these ASCs specialize in secreting important amounts of antibodies and usually lose other functionalities of naïve B cells. This differentiation process is scarcely characterized in teleost fish, in which B cells have been shown to share many functional and phenotypic characteristics of mammalian B1 innate subsets. In this context, we were prompted to investigate further the functionalities of ASCs in teleosts, using rainbow trout (Oncorhynchus mykiss) as a model. Our results demonstrate that IgM+ plasma-like cells in the rainbow trout head kidney exhibit a strong IgM secreting capacity along with phagocytic and antigen-presenting capacities, even higher than those of naïve B cells. These IgM+ plasma-like cells were capable of surviving in vitro for 2 wk secreting IgM. Interestingly, they retained a functional B cell receptor that responded to TNP conjugated to lipopolysaccharide, a thymus-independent model antigen, which also rendered these cells more reactive to B cell receptor crosslinking. These findings shed light on the differentiation process of teleost B cells, demonstrating that teleost plasma-like cells conserve other phenotypical attributes beyond immunoglobulin secretion, being capable of directly responding to antigens. These findings point to an exclusive differentiation process of teleost B cells, which might provide mechanistic insights on how mammalian innate subsets such as B1 cells or IgM-expressing plasma cells differentiate.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"40-54"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Memory-like NK cell differentiation, inhibitory NKG2A blockade, and improved recognition via antibody or CAR engineering combine to enhance NK cell attack against multiple myeloma. 记忆样NK细胞分化，抑制NKG2A阻断，以及通过抗体或CAR工程提高识别，共同增强NK细胞对多发性骨髓瘤的攻击。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 DOI: 10.1093/jimmun/vkae004

Alice Y Zhou, Nancy D Marin, Sadia Afrin, Pamela Wong, Jennifer Tran, Miriam T Jacobs, Michelle Becker-Hapak, Lynne Marsala, Mark Foster, Jennifer A Foltz, Carly C Neal, David A Russler-Germain, Lyra Morina, Yeeun Paik, Celia C Cubitt, Timothy Schappe, Patrick Pence, Ethan McClain, Sarah Kelley, Julie Fortier, Mark Fiala, Michael Slade, Mark Schroeder, Keith Stockerl-Goldstein, Ravi Vij, Feng Gao, Melissa M Berrien-Elliott, Todd A Fehniger

{"title":"Memory-like NK cell differentiation, inhibitory NKG2A blockade, and improved recognition via antibody or CAR engineering combine to enhance NK cell attack against multiple myeloma.","authors":"Alice Y Zhou, Nancy D Marin, Sadia Afrin, Pamela Wong, Jennifer Tran, Miriam T Jacobs, Michelle Becker-Hapak, Lynne Marsala, Mark Foster, Jennifer A Foltz, Carly C Neal, David A Russler-Germain, Lyra Morina, Yeeun Paik, Celia C Cubitt, Timothy Schappe, Patrick Pence, Ethan McClain, Sarah Kelley, Julie Fortier, Mark Fiala, Michael Slade, Mark Schroeder, Keith Stockerl-Goldstein, Ravi Vij, Feng Gao, Melissa M Berrien-Elliott, Todd A Fehniger","doi":"10.1093/jimmun/vkae004","DOIUrl":"10.1093/jimmun/vkae004","url":null,"abstract":"Natural killer (NK) cells are a promising approach for cellular cancer immunotherapy and are being investigated to treat patients with multiple myeloma (MM). We found that MM patient blood NK cell frequencies were normal with increased activating receptors and cytotoxic granules, without evidence of functional exhaustion. Despite this activated state, MM target cells were resistant to conventional NK cells by unclear mechanisms. Memory-like (ML) NK cells are generated after brief activation via the interleukin (IL)-12, IL-15, and IL-18 receptors and exhibit multiple enhanced antitumor properties. ML NK cell differentiation improved healthy donor and MM patient NK cell responses against MM target cells, in vitro and in vivo in immunodeficient murine xenograft models. Moreover, incorporating NKG2A checkpoint blockade to overcome HLA-E-induced inhibition further enhanced ML NK cell responses against MM in vitro and in vivo. Because activating receptor recognition of MM by ML NK cells was inadequate, strategies to improve this were investigated. Utilizing anti-SLAMF7 monoclonal antibody (elotuzumab) or anti-BCMA chimeric antigen receptors resulted in robust increases in ML NK cell functional responses against MM. In summary, ML differentiation enhances NK cell attack against myeloma, and combination with approaches to block inhibitory checkpoints and promote MM-specific activation are promising translational NK cell strategies for MM immunotherapy.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2. 猫MHC I类冠状病毒肽的精确基序和交叉呈现：对SARS-CoV-2轻度感染的影响

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 DOI: 10.1093/jimmun/vkae006

Peiwen Qiao, Can Yue, Weiyu Peng, Kefang Liu, Shuting Huo, Di Zhang, Yan Chai, Jianxun Qi, Zeyu Sun, George F Gao, Guizhen Wu, Jun Liu

{"title":"Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.","authors":"Peiwen Qiao, Can Yue, Weiyu Peng, Kefang Liu, Shuting Huo, Di Zhang, Yan Chai, Jianxun Qi, Zeyu Sun, George F Gao, Guizhen Wu, Jun Liu","doi":"10.1093/jimmun/vkae006","DOIUrl":"https://doi.org/10.1093/jimmun/vkae006","url":null,"abstract":"As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein. The possibility of cross-presentation is further supported by the similar conformation of the corresponding peptides KP-CoV-9 (RSFIEDLLF) and KM-FECV-9 (RSAVEDLLF) from the 2 coronaviruses presented by FLA-K*00701. Our findings provide insights into the understanding of the cross-presentation of peptides from SARS-CoV-2 and feline coronaviruses FECV and the development of universal vaccine for coronaviruses.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"115-129"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune suppression sustained allograft acceptance requires PD1 inhibition of CD8+ T cells. 免疫抑制持续的同种异体移植物接受需要PD1抑制CD8+ T细胞。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-01-01 DOI: 10.1093/jimmun/vkae007

Hilary Miller-Handley, Gavin Harper, Giang Pham, Lucien H Turner, Tzu-Yu Shao, Abigail E Russi, John J Erickson, Mandy L Ford, Koichi Araki, Sing Sing Way

{"title":"Immune suppression sustained allograft acceptance requires PD1 inhibition of CD8+ T cells.","authors":"Hilary Miller-Handley, Gavin Harper, Giang Pham, Lucien H Turner, Tzu-Yu Shao, Abigail E Russi, John J Erickson, Mandy L Ford, Koichi Araki, Sing Sing Way","doi":"10.1093/jimmun/vkae007","DOIUrl":"10.1093/jimmun/vkae007","url":null,"abstract":"Organ transplant recipients require continual immune-suppressive therapies to sustain allograft acceptance. Although medication nonadherence is a major cause of rejection, the mechanisms responsible for graft loss in this clinically relevant context among individuals with preceding graft acceptance remain uncertain. Here, we demonstrate that skin allograft acceptance in mice maintained with clinically relevant immune-suppressive therapies, tacrolimus and mycophenolate, sensitizes hypofunctional PD1hi graft-specific CD8+ T cells. Uninterrupted immune-suppressive therapy is required because drug discontinuation triggers allograft rejection, replicating the requirement for immune-suppressive therapy adherence in transplant recipients. Graft-specific CD8+ T cells in allograft-accepted mice show diminished effector differentiation and cytokine production, with reciprocally increased PD1 expression. Allograft acceptance-induced PD1 expression is essential, as PDL1 blockade reinvigorates graft-specific CD8+ T cell activation with ensuing allograft rejection despite continual immune-suppressive therapy. Thus, PD1 sustained CD8+ T cell inhibition is essential for allograft acceptance maintained by tacrolimus plus mycophenolate. This necessity for PD1 in sustaining allograft acceptance explains the high rates of rejection in transplant recipients with cancer administered immune checkpoint inhibitors targeting PD1/PDL1, highlighting shared immune suppression pathways exploited by tumor cells and current therapies for averting allograft rejection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"192-198"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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