ANTIGEN RECOGNITION AND RESPONSES
Ubiquitination of MHC Class II Is Required for Development of Regulatory but Not Conventional CD4+ T Cells
MHC II ubiquitination is dispensable for maintenance of conventional CD4+ T cells.
MHC II ubiquitination is required for thymic Treg development.
Lack of MHC II ubiquitination does not provoke autoimmunity.
ITK regulated TCR signal strength and Ag affinity control development of CD8 memory.
Reducing TCR signal strength and Ag affinity enhances CD8 memory development.
TCR signal strength controls cytokine production independent of TCR Ag affinity.
Conditional Silencing of H-2Db Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen–Specific CD8 T Cell Responses during Theiler's Virus Infection
The floxed H-2Db mouse is a new tool for dissecting cell-specific Ag presentation.
Rapid priming of CNS-infiltrating antiviral CD8 T cells requires DCs.
LysM+ APCs are not equivalent to DCs in priming antiviral CD8 T cells.
Peripheral Tolerance Checkpoints Imposed by Ubiquitous Antigen Expression Limit Antigen-Specific B Cell Responses under Strongly Immunogenic Conditions
Bystander innate and adaptive signals can partially breach B cell anergy.
Self-reactive B cells can be recruited at low levels into the GC.
Ab production to self-antigen is rapid but transient and of low affinity.
CLINICAL AND HUMAN IMMUNOLOGY
Confocal imaging microscopy uncovers Tfh cell dynamics in human lymphoid tissues.
Tfh cells show a heterogeneous distribution and migration in GC light zones.
In outer zones, Tfh cells move fast, forming brief homotypic interactions.
Chaperone-Mediated Autophagy Suppresses Apoptosis via Regulation of the Unfolded Protein Response during Chronic Obstructive Pulmonary Disease Pathogenesis
Nrf2 is responsible for regulating CMA activity in COPD lungs.
Reduction of CMA activity causes enhanced UPR-mediated apoptosis in COPD.
Thymic ECs express more MHC I molecules than extrathymic ECs.
Aire, Nlrc5, Stat1, and IFN-λ enhance constitutive MHC I expression in thymic ECs.
Herpes Simplex Virus Type 2 Inhibits Type I IFN Signaling Mediated by the Novel E3 Ubiquitin Protein Ligase Activity of Viral Protein ICP22
HSV-2 inhibits type I IFN signaling mediated by viral protein ICP22.
ICP22 functions as a novel E3 ubiquitin protein ligase to degrade ISGF3.
A Novel Cochlioquinone Derivative, CoB1, Regulates Autophagy in Pseudomonas aeruginosa Infection through the PAK1/Akt1/mTOR Signaling Pathway
A novel cochlioquinone B derivative, CoB1, was purified.
CoB1 induces autophagy in mouse AMs against PAO1 infection.
CoB1 regulates autophagy through the PAK1/Akt1/mTOR signaling pathway.
IMMUNE SYSTEM DEVELOPMENT
SWAP-70 and DEF6 are novel regulatory factors in DC differentiation.
Both factors act at separate stages in early DC precursors.
SWAP-70 and DEF6 regulate the functional maturation status of migDCs.
An Ig γ Marker Genotype Is a Strong Risk Factor for Alzheimer Disease, Independent of Apolipoprotein E ε4 Genotype
GM 17/17 genotype was associated with a 4-fold increased risk of AD.
Association is independent of apolipoprotein E ε4 genotype and other AD risk genes.
Results unify the viral (HSV1) and genetic etiologies of AD.
Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease
KIR3DL1 and HLA-Bw4 are associated with different PD clinical features.
Highly expressing KIR3DL1 variants protect against the more debilitating symptoms of PD.
IMMUNOTHERAPY AND VACCINES
Protective Immune Responses Elicited by Deglycosylated Live-Attenuated Simian Immunodeficiency Virus Vaccine Are Associated with IL-15 Effector Functions
Deglycosylated SIV vaccine elicited protective response against heterologous SIV.
SIV-specific CD8+ T cells did not account for the protective response.
IL-15–responding NK and CD8+ T cells were associated with the protective response.
Highly diluted Abs to IFN-γ induce conformational changes in IFN-γ.
Highly diluted Abs to IFN-γ improve binding of IFN-γ to the IFN-γ receptor.
Highly diluted Abs to IFN-γ increase survival of mice with influenza A infection.
INFECTIOUS DISEASE AND HOST RESPONSE
Identification of a Protective Leishmania Antigen Dihydrolipoyl Dehydrogenase and Its Responding CD4+ T Cells at Clonal Level
A naturally processed L. major peptide was identified and used to make a tetramer.
DLD-specific CD4+ T cells produce effector cytokines and display memory function.
Vaccination with rDLD protein induces strong protection against virulent challenge.
INNATE IMMUNITY AND INFLAMMATION
ArhGAP15, a RacGAP, Acts as a Temporal Signaling Regulator of Mac-1 Affinity in Sterile Inflammation
Deficiency of ArhGAP15 leads to increased affinity of integrin Mac-1 on leukocytes.
ArhGAP15 affects leukocyte recruitment by control of postadhesion steps.
B Lymphocyte–Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury
AKI is a serious condition affecting one fifth of hospital patients.
In AKI, B cells produce CCL7 and facilitate neutrophil and monocyte recruitment.
CCL7 blockade in mice reduces myeloid cell infiltration and ameliorates AKI.
MBL interacts with bound β2-GPI.
The MBL/β2-GPI complex activates the lectin pathway of the complement system.
Complement activated by the MBL/β2-GPI complex promotes thrombin generation.
NLRP3 Inflammasome Activation in Lung Vascular Endothelial Cells Contributes to Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury
Deficiency of NLRP3 inflammasome and IL-1β prolongs survival after intestinal I/R.
NLRP3 inflammasome in LVECs plays an important role in intestinal I/R-induced ALI.
I/R-derived lipid mediators enhance NLRP3 inflammasome activation in LVECs.
Disease Risk–Associated Genetic Variants in STAT1 and STAT4 Function in a Complementary Manner to Increase Pattern-Recognition Receptor–Induced Outcomes in Human Macrophages
A disease-associated genetic variant regulates expression of both STAT1 and STAT4.
STAT1/STAT4 regulate autocrine/paracrine cytokine responses to microbial products.
STAT1/STAT4 cooperate to regulate antimicrobial pathways in human macrophages.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development
BioID analysis reveals extensive transcription factor interactions.
GATA3 and TCF7 share binding sites with ARID1a in T cell progenitors.
ARID1a is essential for normal T cell development.
G-CSFR blockade with VR81 mAb is highly protective in a mouse model of renal IRI.
VR81 mAb reduces tubular injury, innate cell infiltration, and complement activation.
IR-induced changes in renal gene expression are prevented by VR81 mAb treatment.
Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution
PTCY + ATG versus PTCY limits the occurrence of grade 2–4 acute GVHD after RIC PBSC h-HSCT.
Quicker reconstitution of some NK cell subtypes may help to avoid relapse.
Adoptive T Cell Therapy with IL-12–Preconditioned Low-Avidity T Cells Prevents Exhaustion and Results in Enhanced T Cell Activation, Enhanced Tumor Clearance, and Decreased Risk for Autoimmunity
Low-avidity T cells provide poor tumor control and exhibit an exhausted phenotype.
IL-12 cytokine priming corrects low-avidity T cell defects and prevents exhaustion.
Low- and high-avidity T cells function equivalently with increased tumor Ag.
Macrophage function is modulated by the surrounding ECM protein collagen.
A high collagen density makes macrophages more immunosuppressive.
Collagen could affect the immunosuppressive nature of tumor-associated macrophages.
Correction: Bcl2L12 Contributes to Th2-Biased Inflammation in the Intestinal Mucosa by Regulating CD4+ T Cell Activities
On the cover: The image shows the structure of the small dimeric protein IFN-γ. The amino acid side chains highlighted are those most affected by conformational changes upon its interaction with highly diluted anti–IFN-γ. These changes were identified by high-resolution solution nuclear magnetic resonance spectroscopy. Tarasov, S. A., E. A. Gorbunov, E. S. Don, A. G. Emelyanova, A. L. Kovalchuk, N. Yanamala, A. S. S. Schleker, J. Klein-Seetharaman, R. Groenestein, J.-P. Tafani, P. van der Meide, and O. I. Epstein. 2020. Insights into the mechanism of action of highly diluted biologics. J. Immunol. 205: 1345–1354.
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