Biology subjects

Campbell, D. J.

Publications and source records attributed to Campbell, D. J..

18 recordsLinked to original sources

bioRxiv2026

Establishing an ex vivo platform for molecular profiling of skin structural cells using frozen human skin biopsies

Skin structural cells, including keratinocytes, melanocytes, endothelial cells, and fibroblasts, play critical roles in the development of chronic inflammatory skin disease. Inflammatory stimuli induce transcriptional reprogramming and epigenetic changes in skin structural cells, which contribute to disease pathogenesis. Although two-dimensional (2D) and three-dimensional (3D) skin culture models have been widely used to investigate inflammatory responses in skin structural cells, ex vivo systems that maintain skin structure and cellular composition remain limited. To address this gap, we explored using frozen skin biopsies as an experimental platform to study the responses of skin structural cells to inflammatory stimuli. Using a simple air-liquid interface culture method on permeable Transwell inserts, we showed that viable skin structural cells that retain cell-type-specific transcriptional profiles can be recovered from frozen skin biopsies after prolonged in vitro culture. Stimulation with IFN-{gamma} induced robust transcriptional and chromatin accessibility changes that were largely resolved after stimulus removal, with transcriptional responses to secondary stimulation comparable to the primary stimulation. Treatment of cultured skin biopsies with histone-modifying enzyme inhibitors effectively altered global histone modification levels, but did not substantially affect the transcriptional resolution of IFN-{gamma}-induced responses. Collectively, these findings establish cryopreserved human skin biopsies as a scalable ex vivo platform that enables mechanistic studies of inflammatory responses of multiple populations of skin structural cells.

immunology↗

bioRxiv2026

Homeostatic fibroblast niche collapse in clinically uninvolved skin marks a pre-fibrotic stage of systemic sclerosis

Systemic sclerosis, or scleroderma, is a chronic autoimmune disease characterized by vasculopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Heterogeneous clinical presentation and polygenic risk complicate our understanding of disease mechanisms and the path to effective therapy. Single-cell analyses have revealed substantial transcriptional diversity in skin, but disease-associated reprogramming remains poorly defined. To address this, we performed high-resolution spatial transcriptomic profiling of paired clinically uninvolved and clinically affected scleroderma donor skin alongside healthy controls. We identified a continuum of cellular, molecular, and spatial changes to the stroma that were already evident in clinically uninvolved tissue yet still distinct from the broader and more advanced changes in paired fibrotic samples. Uninvolved skin was comparable to healthy tissue by clinical and histopathological assessment, but distinguishable by the numerical reduction, transcriptional reprogramming, and spatial isolation of LGR5+SCARA5+PI16+ progenitor fibroblasts. In parallel, the dermal vascular smooth muscle compartment shifted from a contractile to a synthetic, activated state, suggesting reprogramming that begins before overt fibrosis. Cell neighborhood analysis revealed that progenitor fibroblasts occupy dense stromal niches in healthy skin that collapse in clinically uninvolved tissue, replaced by isolated, disease-associated cellular networks. These data indicate that clinically uninvolved skin occupies an intermediate stage along the pathologic continuum of scleroderma, establishing a framework for strategies to preserve homeostatic fibroblast niches before tissue remodeling and fibrotic commitment.

immunology↗

bioRxiv2026

Heterogeneity of HCMV-Specific CD8+ T Cells is Established Early in Infection, Clonally Encoded, and Stable Over Time

Human cytomegalovirus (CMV) elicits lifelong memory T cell responses of striking size and phenotypic diversity, but how these diverse responses are established during acute infection and evolve over decades of chronic stimulation is poorly understood. We tracked CD8+ T cells specific for the viral antigens pp65 and IE1 by single-cell RNAseq, TCRseq, and CITEseq over a period of 16 months in a newly seroconverted donor, and in five latently infected donors over intervals ranging from 4.5 to 12.5 years. We found that individual T cell clones exhibited distinct, specificity-dependent transcriptional profiles, with pp65-specific cells skewed toward central memory phenotypes and IE1-specific cells enriched for effector and chronically activated states. Among pp65-specific T cells we identified a CMC1-expressing state not previously described in virus-specific T cells that shares transcriptional features with exhausted T cells in human tumors yet remains phenotypically stable and clonally intact for over a decade of viral latency. Distinct clonal phenotypes arose during acute infection and were remarkably stable during viral latency, and these phenotypes tracked with relative TCR avidity and TCR sequence. Our findings reveal that the phenotypic diversity of the human CMV-specific CD8+ T cell response is organized at the level of individual clones, with distinct functional identities established during acute infection and preserved with striking fidelity across decades of viral latency and chronic antigen exposure.

immunology↗

bioRxiv2026

Type I Interferon-Driven Monocyte Dysregulation and MAS-associated CD8+ T cells During Macrophage Activation Syndrome

Macrophage activation syndrome (MAS) is driven by a hyperinflammatory response characterized by aberrant activation of lymphocytes and phagocytes. While monocytes and macrophages are thought to be important in MAS pathogenesis, their role remains poorly understood. We used bulk and single-cell RNA sequencing (RNA-Seq) on sorted monocytes from children with MAS and healthy controls to identify transcriptional changes during MAS. We defined a MAS signature in classical monocytes that correlated with ferritin and was elevated in monocytes from systemic lupus erythematosus and COVID-19 patients. We also identified a subset of classical monocytes with high levels of interferon-stimulated genes (ISGs) that expanded during MAS. Surprisingly, the transcriptional signature of these cells was driven by type I IFNs, rather than IFN{gamma}. Consistent with this finding, we detected increased levels of circulating IFN{beta} during MAS, suggesting that IFN{beta} plays an unrecognized role in driving MAS monocyte responses. We also identified a MAS-associated CD8+ T cell population with a distinctive transcriptional signature. We used cell-cell communication algorithms to predict increased immunoregulatory interactions between monocytes and T cells during MAS. Together, these results provide new evidence for a role for type I IFN during MAS and identify a unique CD8+ T cell population that may contribute to MAS pathophysiology.

immunology↗

bioRxiv2026

Defects in CD8+ T cell suppression by Foxp3-ΔE2 expressing regulatory T cells

AbstractRegulatory T cells (Tregs) prevent autoimmunity through suppressive functions largely programmed by the transcription factor FOXP3. Healthy humans express approximately equivalent levels of two major alternatively spliced isoforms of FOXP3: a full-length version containing all coding exons (FOXP3-FL) and a version lacking exon 2 (FOXP3-{Delta}E2). However, sole FOXP3-{Delta}E2 expression causes lethal IPEX syndrome, and the FOXP3-{Delta}E2 isoform is elevated in several autoimmune diseases. These observations strongly suggest defects in suppression by FOXP3-{Delta}E2 Tregs which we investigated here using Foxp3-{Delta}E2 mice. In an influenza virus infection model, Foxp3-{Delta}E2 mice had an increased magnitude of the CD8+ T cell response during acute and memory formation phases of infection. Transcriptomic and chromatin accessibility analyses of homeostatic Foxp3-{Delta}E2 Tregs revealed impaired Treg programming, including reduced expression of inhibitory molecules such as Il2ra and chemokine receptors. Decreased cell surface CD25 expression on Foxp3-{Delta}E2 Tregs was associated with reduced IL-2 responsiveness in Foxp3-{Delta}E2 Tregs and, reciprocally, increased IL-2 responsiveness in CD8+ T cells from Foxp3-{Delta}E2 mice. Additionally, altered chemokine receptor expression resulted in diminished localization of Foxp3-{Delta}E2 Tregs to the T cell zone of the inflamed lymph node. Thus, Treg programming by the Foxp3-{Delta}E2 isoform impairs suppressive function, resulting in failure to restrain CD8+ T cells and aberrant immune responses. One Sentence SummaryFoxp3-{Delta}E2 expressing regulatory T cells have altered cellular programming which impairs their IL-2 sink function and co-localization with conventional T cells during priming, enhancing CD8+ T cell responses.

immunology↗

bioRxiv2025

The altered T cell landscape in Systemic Sclerosis patients is characterized by dysfunctional type 1 immunity.

BackgroundT cells in patients with chronic autoimmunity show features of dysfunction and exhaustion. However, the functionally-defined T cell subsets affected by these changes remain poorly characterized. Here, we sought to reveal aberrations in the composition, phenotype and function of canonical T cell subsets in the blood of Systemic Sclerosis (SSc) patients, compared to healthy subjects and Systemic Lupus Erythematosus (SLE) patients. MethodsWe developed a novel multidimensional flow-cytometry panel to simultaneously detect lineage-defining transcription factors, co-inhibitory receptors and other functional markers to characterize T cell subsets without in vitro restimulation. We compared T cell landscapes in SSc and SLE patients, and healthy subjects, using Optimized t-SNE and PhenoGraph algorithms. Cytokine production in patient samples was determined using intracellular cytokine staining. Transcriptomic analysis was performed to assess the role of IFN-{gamma} in fibroblasts. ResultsThe data show altered distribution and aberrant functional states of transcription factor-defined T cell subsets in patients with autoimmunity, with shared and unique features between diseases and their subtypes. Strikingly, SSc and SLE patients showed a severe deficiency in subsets of CD8+ and CD4-CD8- T cells that expressed T-bet, which is critical for IFN-{gamma}-dependent type 1 immunity, and exhibited features of exhaustion. Moreover, TIGIT+Foxp3+ regulatory T cells, known to suppress Th1 responses, were selectively increased in SSc. Functionally, T cells from SSc patients produced less IFN-{gamma}, a cytokine that suppresses pro-fibrotic gene expression in fibroblasts. ConclusionOur study demonstrates that SSc patients have a defective IFN-{gamma}-producing T cell compartment that may lead to reduced anti-fibrotic T cell activity, enabling chronic fibrosis development. FundingNational Institute of Allergy and Infectious Diseases/NIH, National Institute of Arthritis and Musculoskeletal Diseases/NIH, National Heart, Lung and Blood Institute/NIH, National Scleroderma Foundation, National Jewish Health

immunology↗

bioRxiv2025

Loss of the actin remodeling protein Flightless-1 impairs CD8 and regulatory T cell function

T cell immunity depends on the precise coordination of signaling networks with actin cytoskeleton remodeling, yet the molecular regulators of these processes remain incompletely defined. Flightless-1 (FLII) is a gelsolin-family actin regulator with unique leucine-rich repeats that can couple cytoskeletal dynamics to diverse signaling pathways. Here, using conditional knockout mice, we identify essential roles for FLII in both CD8+ and regulatory T cells. Loss of FLII in CD8+ T cells caused a profound loss of naive cells from the spleen, impaired CCR7-dependent migration, and defective accumulation in the lung parenchyma during antigen-specific responses to respiratory vesicular stomatitis virus infection, despite largely preserved activation, effector differentiation, and cytotoxic function. FLII-deficient Foxp3+ regulatory T cells maintained normal numbers but exhibited diminished CD25 expression, defective IL-2 signaling, and failed to restrain spontaneous, tissue-specific autoimmunity. These findings identify FLII as a critical and previously unrecognized orchestrator of T cell trafficking and immune regulation, which may link chemokine receptor signaling to actin remodeling and is essential for proper T cell migration and function.

immunology↗

bioRxiv2025

Divergent effects of a Treg selective IL-2 mutein on Influenza-specific T cell responses

Enhancing regulatory T cell (Treg) function offers a compelling therapeutic strategy for autoimmune disease. Engineered IL-2 muteins selectively expand functional Tregs with minimal impact on other immune cells, but their potential to compromise antiviral immunity remains largely unexplored. Here, we used a murine model of Influenza A virus (Flu) infection to determine how IL-2 mutein shapes T cell responses to respiratory virus infection. IL-2 mutein administration prior to infection suppressed Flu-specific (Flu-sp) CD8 T cell responses and altered their localization and phenotype within the lungs, without affecting bystander CD8 T cells. This suppression correlated with reduced antigen presentation molecule expression on conventional dendritic cells (cDCs) early after infection but did not impact Flu-sp CD8 T cell priming. In contrast, administering IL-2 mutein during infection exacerbated disease and drove CD25-dependent expansion of Flu-sp CD8 T cells. Despite these opposing effects on effector responses, Fc.Mut24-treated mice generated robust antibody responses and protective T cell memory which were maintained for at least 170 days. These findings reveal that Fc.Mut24 has temporally distinct effects on antiviral immunity, dampening early effector responses when given before infection, but enhancing effector expansion and disease severity when delivered during infection. Our results provide critical context for the therapeutic application of IL-2 muteins and highlight the importance of treatment timing in balancing immune modulation with protective immunity.

immunology↗

bioRxiv2024

T cells promote distinct transcriptional programs of cutaneous inflammatory disease in human skin structural cells

T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cells precipitate skin pathology occurring alongside altered structural cell frequencies and transcriptional states, but to what extent different T cells promote disease-associated changes remains unclear. We show that functionally diverse circulating and skin-resident CD4+CLA+ T cell populations promote distinct transcriptional outcomes in human keratinocytes and fibroblasts associated with inflamed or healthy tissue. We identify Th17 cell-induced genes in keratinocytes that are enriched in psoriasis patient skin and normalized by anti-IL-17 therapy. We also describe a CD103+ skin-resident T cell-induced transcriptional module enriched in healthy controls that is diminished during psoriasis and scleroderma and show that CD103+ T cell frequencies are altered during disease. Interrogating clinical data using immune-dependent transcriptional signatures defines the T cell subsets and genes distinguishing inflamed from healthy skin and allows investigation of heterogeneous patient responses to biologic therapy. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=35 SRC="FIGDIR/small/606077v4_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@fb573corg.highwire.dtl.DTLVardef@11c4eb3org.highwire.dtl.DTLVardef@17304cforg.highwire.dtl.DTLVardef@40d6ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

An IL-2 mutein increases IL-10 and CTLA-4-dependent suppression of dendritic cells by regulatory T cells

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3+ regulatory T (TR) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated TR population with elevated proliferation, a transcriptional program associated with Stat5- and TCR-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface MHC class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 costimulatory ligands from maturing cDCs to TR cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes resulting in T cell anergy. Thus, IL-2 mutein-expanded TR cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.

immunology↗

bioRxiv2023

Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements

Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority of these signals are located in non-coding regions and likely impact cis-regulatory elements (cRE). Because cRE function is dynamic across cell types and states, profiling the epigenetic status of cRE across physiological processes is necessary to characterize the molecular mechanisms by which autoimmune variants contribute to disease risk. We localized risk variants from 15 autoimmune GWAS to cRE active during TCR-CD28 costimulation of naive human CD4+ T cells. To characterize how dynamic changes in gene expression correlate with cRE activity, we measured transcript levels, chromatin accessibility, and promoter-cRE contacts across three phases of naive CD4+ T cell activation using RNA-seq, ATAC-seq, and HiC. We identified [~]1,200 protein-coding genes physically connected to accessible disease-associated variants at 423 GWAS signals, at least one-third of which are dynamically regulated by activation. From these maps, we functionally validated a novel stretch of evolutionarily conserved intergenic enhancers whose activity is required for activation-induced IL2 gene expression in human and mouse, and is influenced by autoimmune-associated genetic variation. The set of genes implicated by this approach are enriched for genes controlling CD4+ T cell function and genes involved in human inborn errors of immunity, and we pharmacologically validated eight implicated genes as novel regulators of T cell activation. These studies directly show how autoimmune variants and the genes they regulate influence processes involved in CD4+ T cell proliferation and activation.

immunology↗

bioRxiv2020

Designed proteins assemble antibodies into modular nanocages

Antibodies are widely used in biology and medicine, and there has been considerable interest in multivalent antibody formats to increase binding avidity and enhance signaling pathway agonism. However, there are currently no general approaches for forming precisely oriented antibody assemblies with controlled valency. We describe the computational design of two-component nanocages that overcome this limitation by uniting form and function. One structural component is any antibody or Fc fusion and the second is a designed Fc-binding homo-oligomer that drives nanocage assembly. Structures of 8 antibody nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage match the corresponding computational models. Antibody nanocages targeting cell-surface receptors enhance signaling compared to free antibodies or Fc-fusions in DR5-mediated apoptosis, Tie2-mediated angiogenesis, CD40 activation, and T cell proliferation; nanocage assembly also increases SARS-CoV-2 pseudovirus neutralization by -SARS-CoV-2 monoclonal antibodies and Fc-ACE2 fusion proteins. We anticipate that the ability to assemble arbitrary antibodies without need for covalent modification into highly ordered assemblies with different geometries and valencies will have broad impact in biology and medicine.

biochemistry↗

bioRxiv2020

The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity

Despite a rapidly growing body of literature on COVID-19, our understanding of the immune correlates of disease severity, course and outcome remains poor. Using mass cytometry, we assessed the immune landscape in longitudinal whole blood specimens from 59 patients presenting with acute COVID-19, and classified based on maximal disease severity. Hospitalized patients negative for SARS-CoV-2 were used as controls. We found that the immune landscape in COVID-19 forms three dominant clusters, which correlate with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who have a moderate disease course, whereas those with severe disease have features suggestive of a protracted and dysregulated immune response. Further, we identified coordinate immune alterations accompanying clinical improvement and decline that were also seen in patients who received IL-6 pathway blockade. The hospitalized COVID-19 negative cohort allowed us to identify immune alterations that were shared between severe COVID-19 and other critically ill patients. Collectively, our findings indicate that selection of immune interventions should be based in part on disease presentation and early disease trajectory due to the profound differences in the immune response in those with mild to moderate disease and those with the most severe disease.

immunology↗

bioRxiv2020

ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue

A unique population of Foxp3+ regulatory T cells (TR) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. The costimulatory molecule ICOS is highly expressed on effector (e)TR that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream PI3K signaling in limiting the abundance, VAT-associated phenotype, and function of TR specifically in VAT. Icos-/- mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TR to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function. SummaryThe authors demonstrate that loss of ICOS-dependent PI3-kinase signaling supports visceral adipose tissue (VAT) TR abundance and function, and this correlates with reduced adipose inflammation and improved insulin sensitivity after high-fat diet. This work highlights a new molecular pathway that regulates VAT-TR accumulation and activity.

immunology↗

bioRxiv2020

Transcriptomic profiling of human effector and regulatory T cell subsets identifies predictive population signatures

After activation, CD4+ T helper (Th) cells differentiate into functionally specialized populations that coordinate distinct immune responses and protect against different types of pathogens. In humans, these effector and memory Th cell subsets can be readily identified in peripheral blood based on their differential expression of chemokine receptors that govern their homeostatic and inflammatory trafficking. Foxp3+ regulatory T (Treg) cells can also be divided into subsets that phenotypically mirror each of these effector populations, and share expression of key transcription factors and effector cytokines. In this study, we performed comprehensive transcriptional profiling of 11 phenotypically distinct Th and Treg cell subsets sorted from peripheral blood of healthy individuals. Despite their shared phenotypes, we found that mirror Th and Treg subsets were transcriptionally dissimilar, and that Treg cell populations showed limited transcriptional diversity compared to Th cells. We identified core transcriptional signatures shared across all Th and Treg cell populations, and unique signatures that define each of the Th or Treg populations. Finally, we applied these signatures to bulk Th and Treg RNA-seq data and found enrichment of specific Th and Treg cell populations in different human tissues. These results further define the molecular basis for the functional specialization and differentiation of Th and Treg cell populations, and provide a new resource for examining Th and Treg specialization in RNA-seq data.

immunology↗

bioRxiv2019

Regulatory T cell expansion by a highly CD25-dependent IL-2 mutein arrests ongoing autoimmunity

Interleukin-2 (IL-2) controls the homeostasis and function of regulatory T cells (Tregs) and defects in the IL-2 pathway contribute to multiple autoimmune diseases. Although recombinant IL-2 therapy has been efficacious in certain inflammatory conditions, the capacity for IL-2 to also activate inflammatory effector responses highlights the need for IL-2-based therapeutics with improved Treg-specificity. From a panel of rationally designed IL-2 variants, we identified IL-2 muteins with reduced potency and enhanced Treg-selectivity due to increased dependence on the IL-2-receptor component CD25. As an Fc-fused homodimer, the optimal Fc.IL-2 mutein induced selective Treg enrichment and reduced agonism of effector cells across a wide dose range. Furthermore, despite being a weaker agonist, overall Treg growth was greater and more sustained due to reduced receptor-mediated clearance of the Fc.IL-2 mutein compared to Fc-fused wild-type IL-2. Preferential Treg enrichment was also observed in the presence of activated pathogenic T cells in the autoimmune target organ, despite a loss of Treg-selectivity in an IL-2R-proximal response. These features allowed for extended resolution of spontaneous autoimmunity using infrequent dosing schedules. Thus, IL-2 muteins enable efficient, flexible, and targeted control of the autoimmune response. One Sentence SummaryA CD25-dependent IL-2 mutein selectively expands regulatory T cells and provides potent and targeted control of autoimmunity.

immunology↗

bioRxiv2019

Treg cells maintain selective access to IL-2 and immune homeostasis despite substantially reduced CD25 function

Interleukin-2 (IL-2) is a critical regulator of immune homeostasis through its impact on both regulatory T (Treg) and effector T (Teff) cells. However, the precise role of IL-2 in the maintenance and function of Treg cells in the adult peripheral immune system remains unclear. Here, we report that neutralization of IL-2 abrogated all IL-2 receptor signaling in Treg cells, resulting in rapid dendritic cell (DC) activation and subsequent Teff cell proliferation. By contrast, despite substantially reduced IL-2 sensitivity, Treg cells maintained selective IL-2 signaling and prevented immune dysregulation following treatment with the inhibitory anti-CD25 antibody PC61, even when CD25hi Treg cells were depleted. Thus, despite severely curtailed CD25 expression and function, Treg cells retain selective access to IL-2 that supports their anti-inflammatory functions in vivo. Antibody-mediated targeting of CD25 is being actively pursued for treatment of autoimmune disease and preventing allograft rejection, and our findings help inform therapeutic manipulation and design for optimal patient outcomes.

immunology↗

bioRxiv2018

Circulating CD4+ memory T cells give rise to a CD69+ resident memory T cell population in non-inflamed human skin

The blood of human adults contains a pool of circulating CD4+ memory T cells and normal human skin contains a CD4+CD69+ memory T cell population that produce IL17 in response to Candida albicans. Here we studied the generation of CD4+CD69+ memory T cells in human skin from a pool of circulating CD4+ memory T cells.\n\nUsing adoptive transfer of human PBMC into a skin-humanized mouse model we discovered the generation of CD4+CD69+ resident memory T cells in human skin in absence of infection or inflammation. These CD4+CD69+ resident memory T cells were activated and displayed heightened effector function in response to Candida albicans. These studies demonstrate that a CD4+CD69+ T cell population can be established in human skin from a pool of circulating CD4+ memory T cells in absence of infection/inflammation. The described process might be a novel way to spread antigen-specific immunity at large barrier sites even in absence of infection or inflammation.

immunology↗