New Zealand had no people or four-footed mammals of any size until it was colonised by Polynesian voyagers and Pacific rats in c. 1280 AD. Between 1769 and 1920 AD, Europeans brought three more ...species of commensal rats and mice, and three predatory mustelids, plus rabbits, house cats hedgehogs and Australian brushtail possums. All have in turn invaded the whole country and many offshore islands in huge abundance, at least initially. Three species are now reduced to remnant populations, but the other eight remain widely distributed. They comprise an artificial but interacting and fully functional bottom-up predator-prey system, responding at all levels to interspecific competition, habitat quality and periodic resource pulsing.
The strength of interactions between T cell receptors and the peptide-major histocompatibility complex (pMHC) directly modulates T cell fitness, clonal expansion, and acquisition of effector ...properties. Here we show that asymmetric T cell division is an important mechanistic link between increased signal strength, effector differentiation, and the ability to induce tissue pathology. Recognition of pMHC above a threshold affinity drove responding T cells into asymmetric cell division. The ensuing proximal daughters underwent extensive division and differentiated into short-lived effector cells expressing the integrin VLA-4, allowing the activated T cell to infiltrate and mediate destruction of peripheral target tissues. In contrast, T cells activated by below-threshold antigens underwent symmetric division, leading to abortive clonal expansion and failure to fully differentiate into tissue-infiltrating effector cells. Antigen affinity and asymmetric division are important factors that regulate fate specification in CD8+ T cells and predict the potential of a self-reactive T cell to mediate tissue pathology.
► Antigens above a specific affinity threshold induce asymmetric T cell division ► Proximal daughter T cells efficiently differentiate into tissue-infiltrating SLECs ► Below-threshold antigens induce symmetric division and few tissue infiltrating SLECs
During the last 10 years, a population of clonally expanded T cells that take up permanent residence in non-lymphoid tissues has been identified. The localization of these tissue resident memory ...(TRM) cells allows them to rapidly respond at the site of antigen exposure, making them an attractive therapeutic target for various immune interventions. Although most studies have focused on understanding the biology underlying CD8 TRMs, CD4 T cells actually far outnumber CD8 T cells in barrier tissues such as lung and skin. Depending on the immune context, CD4 TRM can contribute to immune protection, pathology, or tissue remodeling. Although the ability of CD4 T cells to differentiate into heterogeneous effector and memory subsets has been well-established, how this heterogeneity manifests within the TRM compartment and within different tissues is just beginning to be elucidated. In this review we will discuss our current understanding of how CD4 TRMs are generated and maintained as well as a potential role for CD4 TRM plasticity in mediating the balance between beneficial and pathogenic immune responses.
T-cell–B-cell collaboration in the lung Naderi, Wadschma; Schreiner, David; King, Carolyn G
Current opinion in immunology,
April 2023, 2023-04-00, 20230401, Letnik:
81
Journal Article
Recenzirano
Odprti dostop
Collaboration between T and B cells in secondary lymphoid organs is a crucial component of adaptive immunity, but lymphocytes also persist in other tissues. Recent studies have examined T-cell–B-cell ...interactions in nonlymphoid tissues such as the lung. CD4+ T- resident helper cells (TRH) remain in the lung after influenza infection and support both resident CD8 T cells and B cells. Multiple lung-resident B-cell subsets (B-resident memory (BRM)) that exhibit spatial and phenotypic diversity have also been described. Though not generated by all types of infection, inducible bronchus-associated lymphoid tissue offers a logical place for T and B cells to interact. Perturbations to BRM and TRH cells elicit effects specific to Immunoglobulin A (IgA) production, an antibody isotype with privileged access to mucosa. Understanding the interplay of lymphocytes in mucosal tissues, which can be insulated from systemic immune responses, may improve the design of future vaccines and therapies.
•Protective collaboration between T and B cells occurs in mucosal tissues.•Diverse lymphocyte subsets localize to different parts of the lung.•Lymphocyte collaboration helps clear pathogens and protect against reinfection.•Understanding of resident immune cells will help design vaccines and treatments.
The widespread perception of New Zealand is of a group of remote islands dominated by reptiles and birds, with no native mammals except a few bats. In fact, the islands themselves are only part of a ...wider New Zealand Region which includes a large section of Antarctica. In total, the New Zealand Region has at least 63 recognised taxa (species, subspecies and distinguishable clades) of living native mammals, only six of which are bats. The rest comprise a large and vigorous assemblage of 57 native marine mammals (9 pinnipeds and 48 cetaceans), protected from human knowledge until only a few centuries ago by their extreme isolation in the southwestern Pacific Ocean. Even after humans first began to colonise the New Zealand archipelago in about 1280 AD, most of the native marine mammals remained unfamiliar because they are seldom seen from the shore. This paper describes the huge contrast between the history and biogeography of the tiny fauna of New Zealand’s native land mammals versus the richly diverse and little-known assemblage of marine mammals.
How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial ...infections and that these increased acetate concentrations are required for optimal memory CD8+ T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8+ T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8+ T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8+ T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8+ T cells and translate into increased glycolytic and functional capacity. The immune system thus directly relates systemic metabolism with immune alertness.
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•Serum acetate levels rapidly increase following systemic bacterial infection•Memory CD8+ T cells take up acetate and expand their acetyl-CoA pool•Increased acetyl-CoA levels catalyze functional activity of GAPDH by acetylation•Augmented glycolytic flux rates boost rapid recall responses of memory CD8+ T cells
How systemic metabolic alterations during acute infections impact immune-cell function remains poorly understood. Hess and colleagues demonstrate that acetate rapidly increases during infections, which drives acetylation of GAPDH in memory CD8+ T cells and thereby catalyzes the rapid recall response.
Nonstructural carbohydrate (NSC) remobilization remains poorly understood in trees. In particular, it remains unclear (i) which tissues (e.g., living bark or xylem) and compounds (sugars or starch) ...in woody plants are the main sources of remobilized carbon, (ii) to what extent these NSC pools can be depleted and (iii) whether initial NSC mass or concentration is a better predictor of regrowth potential following disturbance. To address these questions, we collected root segments from a large mature trembling aspen stand; we then allowed them to resprout (sucker) in the dark and remobilize NSC until all sprouts had died. We found that initial starch mass, not concentration, was the best predictor of subsequent sprout mass. In total, more NSC mass (~4×) was remobilized from the living inner bark than the xylem of the roots. After resprouting, root starch was generally depleted to <0.6% w/w in both tissues. In contrast, a large portion of sugars appear unavailable for remobilization: sugar concentrations were only reduced to 12% w/w in the bark and 2% in the xylem. These findings suggest that in order to test whether plant processes like resprouting are limited by storage we need to (i) measure storage in the living bark, not just the xylem, (ii) consider storage pool size-not just concentration-and (iii) carefully determine which compounds are actually components of the storage pool.
In the thymus, high-affinity, self-reactive thymocytes are eliminated from the pool of developing T cells, generating central tolerance. Here, we investigate how developing T cells measure ...self-antigen affinity. We show that very few CD4 or CD8 coreceptor molecules are coupled with the signal-initiating kinase, Lck. To initiate signaling, an antigen-engaged T cell receptor (TCR) scans multiple coreceptor molecules to find one that is coupled to Lck; this is the first and rate-limiting step in a kinetic proofreading chain of events that eventually leads to TCR triggering and negative selection. MHCII-restricted TCRs require a shorter antigen dwell time (0.2 s) to initiate negative selection compared to MHCI-restricted TCRs (0.9 s) because more CD4 coreceptors are Lck-loaded compared to CD8. We generated a model (Lck come&stay/signal duration) that accurately predicts the observed differences in antigen dwell-time thresholds used by MHCI- and MHCII-restricted thymocytes to initiate negative selection and generate self-tolerance.
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•TCR scans multiple coreceptors to initiate a TCR signal and negative selection•Frequency of Lck loaded coreceptors sets antigen dwell-time threshold•Shorter antigen dwell-time threshold for pMHCII compared to pMHCI self-antigens•“Lck come&stay/signal duration” model explains how the TCR reads antigen dwell time
A combination of experimental approaches and mathematic modeling reveals how T cells measure affinity for self-antigens in the thymus to generate self-tolerance.
This paper describes one of the world’s first large-scale experiments in biological control of a major vertebrate pest of agriculture, which was tried in New Zealand during the second half of the ...nineteenth century. Starting from the late 1860s, pasture damage in Southland and Otago by European rabbits was causing serious reductions in productivity of sheep (wool clip and lambing percentages) associated with malnutrition of the breeding ewes, and a consequent decline in the value of pastoral land. In response, and despite repeated local and international warnings, ferrets, stoats and weasels (
Mustela furo
,
M
.
erminea
and
M
.
nivalis
) were liberated on the worst of the rabbit-infested pastures. They were perceived as the ‘natural enemies of the rabbit’ but (unlike foxes) too small to threaten lambs. Over the 50 years after 1870, upwards of 75,000 ferrets, most imported from Australia or locally bred, were released in the South Island. Over the decade 1883–1892, at least 7838 stoats and weasels arrived from Britain. At least 25 shipments are known, with an average of only 10% mortality per shipment. Of the 3585 animals listed by species, 73% were weasels. The total cost of the ferret programme cannot now be estimated; that of stoats and weasels alone was
at least
£5441, probably twice that, or >$NZ 1–2 million in today’s money. Mustelids (and cats) killed many young rabbits, which was helpful because rates of change in rabbit populations are sensitive to variations in juvenile mortality, but in the most rabbit-prone semi-arid lands, mustelids could not remove enough rabbits to prevent the continuing damage to sheep pastures. The era of deliberate introductions of mustelids to control rabbits in New Zealand was short, expensive, and unsuccessful.
The distribution of distinct genetic lineages of mice in New Zealand, combined with historical records of shipping routes, political decisions, market prices, trading patterns and immigration policy, ...suggest that two distinct lineages of Mus musculus travelled separate routes to reach opposite ends of New Zealand in early pre-colonial times (1792–1830). (1) Mus musculus castaneus could have colonised the southern South Island between 1792 and 1810, with sealers returning from the Canton fur market, but these voyages were illegal (=undocumented) because direct trading with China was prohibited until after 1813. Signs that the potential links between the South Island and Canton were seldom used after 1810 include: (a) the Canton sealskin market was already rapidly declining in profitability by the time sealers switched to New Zealand from Bass Strait in 1804; (b) the Otago colonies of fur seals (Arctocephalus forsteri) were exhausted after 1810; (c) M. m. castaneus is absent from the southern offshore islands repeatedly visited by Sydney-based sealers after 1810. (2) M. m. domesticus had multiple well-documented opportunities to colonise the Bay of Islands with traders from Australia after 1821, and both the Cook Strait area and the southern South Island with whalers after 1829. After 1840, multiple haplotypes of M. m. domesticus from different European sources accompanied the organised settlement of New Zealand by European colonists.
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