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Structure-guided protein design enables germline-targeting immunization strategies to generate broadly neutralizing antibodies against MPER, a region of the HIV envelope glycoprotein that is functionally important and highly conserved, but a challenging target for antibody responses.
Batista, Schief and colleagues use a series of germline-targeting immunogens in knock-in mice expressing heavy chain sequences derived from the HIV broadly neutralizing antibody 10E8 to characterize the requirements of 10E8 B cell precursors for entry and maturation in the germinal center.
Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.
Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf− hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf+ stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.
Chronic antigen exposure promotes terminal exhaustion of T cells. Here the authors show a role for TCR stimulation in preserving progenitor exhausted T cells and highlight their TCR-dependent self-renewal during antitumor responses.
Immune cells coordinate β-cell insulin secretion to regulate glucose levels and promote type I interferon production to control systemic viral infection.
Sestan et al. find a conserved mechanism during systemic viral infection in which γδ T cells produce IFNγ to increase pancreatic insulin secretion, lowering blood glucose and then enhancing type I interferon-mediated protection against viral infection.
Segal and colleagues identify a population of immature neutrophils as having regenerative properties on injured neurons and being capable of inducing axon regeneration. These findings suggest potential strategies for restoring lost neurological functions in central nervous system disorders.
Woolf and colleagues use single-cell transcriptomics to determine the gene signature of infiltrating immune cells and potential cell–cell interactions between receptors, ligands, ion channels and metabolites expressed on immune cells and sensory neurons in three models of pain.
CAR T cell technology is being extended beyond the treatment of cancer. New data show that it might also treat allergic asthma, with a single infusion sufficient to prevent pathology for over a year in mice.
Here the authors identify and characterize the development and function of an IFN-γ-producing CD8αβ+ subset of γδ T cells that contributes to malignancy.
CAR T cells have shown great promise in treating some cancers and are now being applied to other diseases. Here the authors engineer mouse and human T cells and show that a single infusion can result in lasting remission from asthma in mice.
The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.
How aging, immunity and cancer are related is incompletely understood. Data now show altered differentiation and loss of function of tumor-infiltrating T cells with aging. So-called TTAD cells seem to be involved.
Cancer and aging are associated with each other, but underlying mechanisms contributing to this correlation are unclear. Here the authors identify a dysfunctional T cell state that is distinct from typical T cell exhaustion and only occurs in the tumor microenvironment during later life.
Our work identifies previously unrecognized functional heterogeneity in tissue-resident interstitial macrophages. We have identified ten macrophage subsets, each thought to specifically contribute to recruiting and organizing cell types within tissues. Moreover, our findings suggest the diversity and division of labor extend to other macrophage populations previously considered homogeneous.