Collaboration between IL-7 and IL-15 enables adaptation of tissue-resident and circulating memory CD8 T cells.

Interleukin-7 (IL-7) is considered a critical regulator of memory CD8 T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (T) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that loss had only a modest effect on persistence of circulating memory and T subsets and that IL-7Rα was primarily required for normal basal proliferation.

CD8 T cell tolerance: It doesn't translate.

The mechanisms that make and break CD8 T cell tolerance to self-antigens remain unclear. In this issue of Immunity, Van Der Byl et al. show that tolerant CD8 T cells rapidly adopt an epigenetically and transcriptionally distinct cell state and exhibit impaired protein translation.

Physiological microbial exposure transiently inhibits mouse lung ILC2 responses to allergens.

Lung group 2 innate lymphoid cells (ILC2s) control the nature of immune responses to airway allergens. Some microbial products, including those that stimulate interferons, block ILC2 activation, but whether this occurs after natural infections or causes durable ILC2 inhibition is unclear. In the present study, we cohoused laboratory and pet store mice as a model of physiological microbial exposure.

Mice with diverse microbial exposure histories as a model for preclinical vaccine testing.

Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination.

CD8 T cell self-tolerance permits responsiveness but limits tissue damage.

Self-specific CD8T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8 T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in , which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/K-specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to -deficient () mice.

The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8 T cells.

Extracellular ATP (eATP) is an ancient 'danger signal' used by eukaryotes to detect cellular damage. In mice and humans, the release of eATP during inflammation or injury stimulates both innate immune activation and chronic pain through the purinergic receptor P2RX7. It is unclear, however, whether this pathway influences the generation of immunological memory, a hallmark of the adaptive immune system that constitutes the basis of vaccines and protective immunity against re-infection.

Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs.

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology.

Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance.

B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4 T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood.

Gut Microbiota Regulates K/BxN Autoimmune Arthritis through Follicular Helper T but Not Th17 Cells.

The bacterial community that colonizes mucosal surfaces helps shape the development and function of the immune system. The K/BxN autoimmune arthritis model is dependent on the microbiota, and particularly on segmented filamentous bacteria, for the autoimmune phenotype. The mechanisms of how the gut microbiota affects arthritis development are not well understood.

Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis.

The antimalarial drug artemisinin and its derivatives exhibit potent immunosuppressive activity in several autoimmune disease models, however the mechanisms are not well-understood. This study was designed to investigate the therapeutic effects and the underlying mechanisms of the artemisinin analog artesunate using the K/BxN mouse model of rheumatoid arthritis. The well-studied disease mechanisms of K/BxN model allowed us to pinpoint the effect of artesunate on disease.

The cellular source and target of IL-21 in K/BxN autoimmune arthritis.

IL-21 is a pluripotent cytokine that regulates B cell and plasma cell differentiation and is thought be an autocrine factor for follicular helper T cell (T(FH)) and Th17 differentiation. Although IL-21 has been implicated in autoimmune diseases, its relevant cellular source and target cells have not been well characterized. We investigated this issue in the K/BxN mouse model of autoimmune arthritis.

Characterization of a human cervical CD4+ T cell subset coexpressing multiple markers of HIV susceptibility.

The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4(+) T cells with enhanced susceptibility, as does expression of the mucosal integrin α4β7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya.

The genotype of early-transmitting HIV gp120s promotes α (4) β(7)-reactivity, revealing α (4) β(7) +/CD4+ T cells as key targets in mucosal transmission.

Mucosal transmission of HIV is inefficient. The virus must breach physical barriers before it infects mucosal CD4+ T cells. Low-level viral replication occurs initially in mucosal CD4+ T cells, but within days high-level replication occurs in Peyer's patches, the gut lamina propria and mesenteric lymph nodes.