The Territories Under Text, History, and Tradition

In two of its major decisions in the 2021–2022 Term, New York State Rifle & Pistol Ass’n v. Bruen and Dobbs v. Jackson Women’s Health Organization, the Court continued solidifying its originalist method of constitutional interpretation by looking increasingly to historical regulatory practice to construe how the Constitution protects individual rights. The Court is focused not only on the original public meaning of constitutional provisions, but also on historical practice. Historical laws and practices are now key to understanding how those who lived at the relevant time thought a constitutional provision might be applied and what regulatory approaches were consistent with that provision. Bruen and Dobbs both considered laws passed by governments in the Western territories prior to statehood in the nineteenth century, but with polar opposite results. One day the Court suggested that territorial laws and practices were exceptional improvisations irrelevant to the search for a national tradition; the very next day, the Court implied that territorial laws can be valuable tools for constitutional interpretation. This Article searches for a more satisfying and consistent theory of how to utilize territorial history in constitutional cases. Part I critically analyzes the decision in Bruen and the Court’s determination that territorial public-carry bans could not serve as analogues to support New York’s modern gun-licensing law. Part II explains the history of continental territories, examines Dobbs and other decisions invoking territorial laws and practices, and identifies relevant principles from legal scholarship regarding the Court’s reliance on non-federal sources to interpret provisions of the U.S. Constitution. Part III argues that the Supreme Court’s use of territorial history in Bruen was inconsistent with its past practice, that territorial history is especially likely to reflect federal constitutional meaning because the territories were subject to the federal Bill of Rights long before those rights were incorporated against state governments, and that a text, history, and tradition methodology should accord territorial laws and practices a meaningful role

Missing Pieces: Gaps in the Record of Early American Decisional Law

In its most recent major Second Amendment decision, New York State Rifle & Pistol Association v. Bruen, the Supreme Court suggested that historical laws “rarely subject to judicial scrutiny” are not especially illuminating because “we do not know the basis of their perceived legality.” Legal scholars have defended Bruen’s approach to historical evidence in part by arguing that the decision requires merely an artificially-limited historical inquiry into internal legal sources to discern overarching principles accepted across the country in the Founding Era. But modern-day lawyers and judges actually know far less than they might believe about whether certain laws were subject to judicial scrutiny during crucial eras of American history because many court decisions—especially from the Founding Era—were simply never recorded for posterity. Those omissions were not random, and they do not represent merely what we today would consider insignificant holdings. Rather, omissions from the surviving record of decisional law are the product of curation by early court reporters, newspaper editors, and other actors often motivated by profit or partisan bias. Therefore, it is often perilous to extrapolate “the general law” from the extant, unrepresentative caselaw that happens to be preserved today. This Essay examines how the non-legal choices and preferences of those who recorded early American case law prior to the gradual emergence of more consistent reporting of judicial decisions in the late nineteenth century shaped the historical record of early decisional law that exists today. Part I chronicles the largely inconsistent and at times chaotic practice of court reporting at and after the Founding and explores how judicial decisions were preserved and published during that time. Part II addresses how modern originalist theories should approach and appreciate the “curated” nature of legal history from that time. I argue that the record of early American decisional law has been profoundly influenced by various actors (legal and non-legal) according to considerations other than preserving an accurate, comprehensive snapshot of “general law” at the time—namely, based on motives including profit and partisanship. This reality, I suggest, means that it is crucial to expand the universe of historical sources when possible to capture what may be missing from the universe of preserved decisional law

Extreme Risk Protection Orders in the Post-Bruen Age: Weighing Evidence, Scholarship, and Rights for a Promising Gun Violence Prevention Tool

Extreme Risk Protection Orders (ERPOs) are civil court orders that temporarily prohibit gun purchase and possession by people who are behaving dangerously and at risk of committing imminent violence. As of September 2023, ERPOs are available in 21 states and the District of Columbia. This Article presents an overview of ERPO laws, the rationale behind their development, and a review and analysis that considers emerging constitutional challenges to these laws (under both the Second Amendment and due process protections) in the post-Bruen era. This Article notes that the presence of multiple constitutional challenges in many ERPO-related cases has confused judicial analysis and argues that, especially in light of Bruen’s novel text, history, and tradition test, courts should be especially careful to clarify how cumulative-rights arguments are impacting their analysis. An examination of Second Amendment court decisions concerning another type of civil protection order, Domestic Violence Protection Orders, informs the approach used to further consider ERPO rights deprivation claims and the constitutionally relevant distinctions among different civil dispossession proceedings. The Article further considers the state of ERPO law in the context of the evolving evidence documenting the uptake and impact of ERPOs on gun violence in the United States, including a review of scholarship that seeks to understand how ERPO statutes are being implemented and to determine whether the laws prevent interpersonal gun violence and suicide. Finally, this Article concludes with a commentary and set of recommendations to inform the practice and future scholarship of ERPO as a tool for preventing gun violence in the United States, in accord with constitutional protections in the post-Bruen age

Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets

Abstract Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naive central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of naive and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.</jats:p

Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo

Abstract The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.</jats:p

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM- CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs. We generated RAG2−/−γc−/− mice in which we replaced the gene encoding mouse TPO by its human homolog. Homozygous humanization of TPO led to increased levels of human engraftment in the bone marrow of the hosts, and multilineage differentiation of hematopoietic cells was improved, with an increased ratio of myelomonocytic verus lymphoid lineages. Moreover, maintenance of human stem and progenitor cells was improved, as demonstrated by serial transplantation. Therefore, RAG2−/−γc−/− TPO-humanized mice represent a useful model to study human hematopoiesis in vivo

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity

Antibody Repertoires in Humanized NOD-scid-IL2Rγnull Mice and Human B Cells Reveals Human-Like Diversification and Tolerance Checkpoints in the Mouse

Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγnull engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγnull mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential DH-JH pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments