Tissue regeneration is viewed as a return to homeostasis, but whether the extracellular matrix (ECM) reverts during recovery from gut inflammation is unclear. Using temporal multi-omics, biomechanical profiling, and spatial fate mapping in colitis models, we showed that colonic ECM underwent lasting pathological reprogramming following inflammation, which we termed modified (mod)ECM. Characterized by collagen XVIII accumulation and immune-driven proteolysis, modECM redirected intestinal stem cells (ISCs) toward a wound-associated epithelial state with a pro-inflammatory transcriptional program. Ex vivo, modECM alone reshaped ISC fate by suppressing Wnt signaling and activating immune recruitment pathways. In vivo, modECM-rich zones sustained T cell infiltration and KRT14+ epithelial cell emergence from Lgr5+ progenitors. This aberrant epithelial program was mirrored in inflamed rectal biopsies from individuals with ulcerative colitis. Our findings redefine the ECM as a long-lived instructive compartment that encodes injury memory and promotes maladaptive regeneration, positioning it as a therapeutic target in chronic inflammatory diseases.

Abstract Intestinal regeneration and host defense require adaptation to environmental cues, but the mechanisms underlying this coordination remain unclear. We show that intestinal Lgr5⁺ stem cells act as luminal sensors via apically localized Toll-like receptor 2 (TLR2), enabling direct detection of microbiota-derived signals. We identify apical TLR2 activation as a mechanism of luminal sensing in adult stem cells and show that it controls epithelial differentiation, antimicrobial peptide production, and crypt organization, with a particularly strong influence on Paneth cell maturation. Genetic ablation of constitutive, epithelial, or stem cell-specific TLR2 disrupts these processes, leading to impaired antimicrobial defense and altered epithelial composition. Using germ-free mice and human intestinal organoids, we demonstrate that this pathway is microbiota-dependent and evolutionarily conserved, respectively. These findings support a model in which stem cells act as active integrators of environmental information and suggest a broader principle by which barrier tissues couple microbial sensing to regeneration and host protection.

The lungs are a major organ of cancer metastasis. Despite advances in the usage of tumor- specific cytotoxic T cells (CTLs) with potent killing activity (i.e., tumor infiltrating T cells, TILs) for killing of primary tumors, how these T cells encounter and kill metastatic lesions at remote organs is still poorly understood. In the present study we compared the ability of potent neoantigen specific CTLs to kill two types of cancer cells that share the same neoantigen and generate distinct metastatic lesions in the lungs of immunocompetent recipient mice. We have used ovalbumin (OVA) as a neoantigen model and found that the OVA-specific OT-I transgenic CD8 CTLs, when intravenously introduced, readily eliminated primary tumors of OVA-expressing breast cancer E0771 cells. Nevertheless, similar OT-I CTLs failed to clear OVA-expressing breast cancer E0771 cells that colonized the lungs. In contrast, similar intravenously introduced OT-I CTLs efficiently eliminated lung metastatic OVA-expressing B16 melanoma cells, ruling out that the intravenous CTLs were exhausted upon entering the lungs. Three-dimensional (3D) imaging of whole lungs revealed that in both experimental and spontaneous metastasis models, the OVA E0771 cells survived inside lung blood vessels but did not recruit circulating OT-I CTLs to their vicinity. Furthermore, canonical vascular adhesion molecules recognized by the CTLs like ICAM-1 and VCAM-1 were not upregulated nearby the lung-residing intravascular E0771 cells as a potential means to recruit lung circulating CTLs to the vicinity of the intravascular tumor cells. Strikingly, the lung residing OVA-expressing E0771 cells lost expression of their OT-I specific OVA-derived SIINFEKL-H-2Kb pMHC complexes while retaining MHC-I expression. This loss was accompanied by a lung-specific transcriptional reduction of key regulators of MHC-I presentation. A temporal loading of OVA-derived SIINFEKL-H-2Kb pMHC complexes on E0771 cells did not result, however, in cancer cell killing inside the lungs. Nevertheless, direct and stable SIINFEKL peptide presentation on these cells overcame their lung specific escape from OT-I mediated killing. Our study is a first indication that subsets of cancer cells that reside in the lungs rapidly downregulate the expression of neoantigen derived peptide MHC-I complexes and thereby evade killing by intravenously introduced tumor antigen-specific CTLs.

Abstract Tuft cells initiate intestinal type 2 immunity, yet the mechanisms that restrain excessive tuft cell activation remain poorly understood. Here, we identify the receptor tyrosine phosphatase CD45 ( Ptprc ), previously considered a hematopoietic marker, as a regulator of intestinal tuft cell function. CD45 expression is restricted to a subset of tuft cells and is induced by helminth infection and IL-13. Epithelial-specific deletion of Ptprc activated a tuft cell inflammatory program, promoted an epithelial inflammatory state, and increased eosinophil accumulation at homeostasis. During Heligmosomoides polygyrus bakeri infection, CD45 deficiency enhanced ILC2 and Th2 responses and reduced parasite burden, demonstrating that epithelial CD45 limits type 2 immunity in vivo . Accordingly, in intestinal organoids, CD45 was dispensable for IL-13-driven tuft cell differentiation but restrained IL-13-responsive transcriptional programs. Mechanistically, CD45-deficient tuft cells exhibited altered protein abundance of STAT5 and IL17RB, implicated in tuft cell immune regulation. Together, these findings identify CD45 as a tuft cell-intrinsic regulatory checkpoint that restrains intestinal type 2 immunity through an IL-13-induced negative-feedback circuit.

Dendritic cells (DCs) cross-present tumor antigens to cognate T cells in tumor-draining lymph nodes (TdLNs). ICAM-1 is a key adhesion molecule involved in the formation of diverse cell-cell contacts between immune cells as well as blood vessels and stromal cells. We have recently found that ICAM-1 expressed by lymph node DCs can stabilize antigen-dependent contacts with naïve CD8 T cells but is dispensable for CD8 T cell differentiation and proliferation into effector and memory lymphocytes generated in various models of vaccination and virus infections. To follow the role of DC ICAM-1 in CD8 proliferation and differentiation triggered by tumor expressed neoantigens, we orthotopically implanted breast cancer E0771 cells expressing the model OVA neoantigen in immunocompetent mice conditionally deleted of ICAM-1 expression in all CD11c expressing -conventional DCs (cDCs), monocyte derived DCs (mDCs) and pDCs. Strikingly, in contrast to viral challenges, the tumor challenge drove naïve tumor-antigen specific CD8 differentiation almost exclusively into T-stem-like central memory T cells (TSL) with high expression of L-selectin (CD62L), PD-1, and the transcription factor TCF-1 implicated in T cell stemness and proliferative potential. Early CD8 activation and differentiation into these central memory T cells remained normal in these mice. This indicated that tumor antigen transfer by migratory DCs to lymph node DCs and its initial cross presentation to naïve T cells do not require ICAM-1 expression by all types of DCs. Furthermore, deletion of ICAM-1 selectively in XCR1 conventional type 1 dendritic cells (cDC1), specialized in tumor antigen uptake and cross priming of tumor specific T cells in tumor draining lymph nodes, did not impair early tumor specific CD8 activation and differentiation. Nevertheless, the maintenance of resident self-renewing stem-like tumor specific CD8 memory cells in the tumor draining lymph nodes was diminished in the absence of ICAM-1 expression by cDC1. We currently explore the possibility that ICAM-1 deficiency in these DCs impairs the stability of survival niches generated by Ag-specific CD8 TSL and cDC1. Our results highlight a specialized instructive role of cDC1 ICAM-1 in antigen dependent maintenance of a pool of lymph node stem-like tumor-specific lymphocytes. This pool is a main source of tumor specific CD8 T cells which egress the draining lymph nodes and home into primary tumors, where they differentiate into short-lived terminally differentiated effector T cells (CTLs) critical for tumor eradication.

RATIONALE The airways of the lung are the primary sites of disease in asthma and cystic fibrosis, chronic diseases that have substantial worldwide disease burden. Airway epithelial cells are crucial first responders to environmental exposures and are implicated in the pathogenesis of these diseases. Our group and others have demonstrated the existence of the pulmonary ionocyte and the ‘hillock’ patches of stratified epithelia in the airway. In addition, we demonstrated that ionocytes and other rare airway epithelial cell-types the tuft cell and pulmonary neuroendocrine cells (PNECs) are directly generated by basal stem cells. Here we examine the contribution of rare cells and hillocks to processes of airway regeneration following injury. METHODS Here we apply single-cell RNA sequencing (scRNA-seq) to the injured mouse trachea after inhalation of sulfur-dioxide (SO2), sampling in a sequential time-course to capture the regeneration process. We apply computational ‘pseudotime’ analysis methods based on recently developed principal graph-based algorithms, and use generalized additive models to identify genes covarying with pseudotime. RESULTS We identify a common basal cell progenitor state for the three rare cell subsets. Analysis of single-cell profiles in transition from this state to each of the three rare cell types identifies genes, and transcription factors that significantly vary along the differentiation trajectory. We observe a significant difference in the abundance of hillock structures between dorsal and ventral basal cells, emphasizing the out-sized role for hillocks in regeneration. Additionally, we infer signaling pathways with roles in cellular specification. CONCLUSIONS These findings revise our understanding of airway regeneration by including the contribution of these previously uncharacterized cell-types and structures in the mouse airway. These results highlight the need to examine the role of these rare cell types in pathogenesis of human respiratory disease.

Neuroendocrine tumors (NETs) occur primarily in the small intestine, lung, and pancreas. Due to their rarity compared to other malignancies in these organs, their complex biology remains poorly understood, including their oncogenesis, tumor composition, and the intriguing phenomena of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). Here, we profiled ten low-grade small intestine NET (SiNET) samples as well as one mixed lung tumor by single-cell or single-nuclei RNA-seq. We find that SiNETs are largely separated into two distinct subtypes, in which the neuroendocrine cells upregulate epithelial or neuronal markers, respectively. Surprisingly, in both subtypes, the neuroendocrine cells are largely non-proliferative while higher proliferation is observed in multiple non-malignant cell types. Specifically, B and plasma cells are highly proliferative in the epithelial-like SiNET subtype, potentially reflecting the outcome of high Migration Inhibitory Factor (MIF) expression in those tumors, which may constitute a relevant target. Finally, our analysis of a mixed lung neuroendocrine tumor identifies a population of putative progenitor cells that may give rise to both neuroendocrine and non-neuroendocrine (squamous) cells, potentially explaining the origin of the mixed histology. Taken together, our results provide important insights and hypotheses regarding the biology of neuroendocrine neoplasms.

Tissue regeneration is conventionally viewed as a return to homeostasis. Here, we uncover that the extracellular matrix (ECM) in the colon undergoes a lasting pathological reprogramming following inflammation, forming a remodeled niche—modECM—that persistently disrupts intestinal stem cell (ISC) identity. Using temporal multi-omics, biomechanical profiling, and spatial fate mapping in murine colitis models, we show that modECM, characterized by Collagen XVIII accumulation and immune-driven proteolysis, redirects ISCs toward a wound-associated, squamous-like epithelial state with pro-inflammatory transcriptional signatures. Ex vivo, modECM alone reprograms ISC fate by suppressing Wnt signaling and activating immune recruitment pathways. In vivo, modECM-rich zones sustain T cell infiltration and KRT14⁺ epithelial cell emergence from Lgr5⁺ progenitors. This aberrant epithelial program is mirrored in inflamed rectal biopsies from ulcerative colitis patients. Our findings redefine the ECM as a long-lived instructive compartment that encodes injury memory and promotes maladaptive regeneration, positioning it as a potential therapeutic target in chronic inflammatory disease. ### Competing Interest Statement The authors have declared no competing interest. Center for New Scientists at the Weizmann Institute of Science Israel Science Foundation, 1587/20, 1800/19 Helen and Martin Kimmel Institute for Stem Cell Research at The Weizmann Institute of Science Minerva Foundation, https://ror.org/0152xm391 Federal German Ministry for Education and Research Moross Integrated Cancer Center Israel Ministry of Science, 4631 Dr. Gilbert S. Omenn and Martha A. Darling Weizmann Institute - Schneider Hospital Fund for Clinical Breakthroughs through Scientific Collaborations Snider Foundation Abisch-Frenkel RNA Therapeutics Center Shimon and Golde Picker grant Weizmann SABRA - Yeda - Sela - WRC Program Estate of Emile Mimran Maurice and Vivienne Wohl Endowment Fellows Herbert K. Bennett Charitable Fund and Dwek Institute for Cancer Therapy Research Cynthia and Andrew Adelson Fund Rose Family Fund for Crohn's and Colitis Research Mireille & Murray Steinberg Family Foundation Thompson Family Foundation Leonard and Carol Berall Foundation

The enteric nervous system (ENS) senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions. However, mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging. Here, we present an optogenetics-integrated gut organ culture system that enables real-time, whole-tissue stimulation of defined ENS lineages, and detailed analysis of their functional impact. We demonstrate that optogenetic activation of enteric cholinergic neurons rapidly modulates intestinal physiology. Interestingly, distinct neuronal firing patterns differentially modulate neuro-immunological gene expression and epithelial barrier integrity. Furthermore, diverse enteric neuronal lineages exert distinct regulatory roles. While cholinergic activation enhances gene-sets associated with type-2 immunity, tachykininergic neurons modulate distinct mucosal defense programs. Intriguingly, luminal introduction of the immunomodulatory bacterium Thomasclavelia ramosa remodeled cholinergic-induced neuro-immunological transcription. These findings suggest that microbial and neuronal signals are locally integrated to fine-tune gut immunity and barrier defense. Collectively, we provide a powerful platform for systematic discovery and mechanistic exploration of functional neuroimmune connections, and their potential modulation by microbes, drugs or metabolites.

Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.

Uncontrolled regeneration leads to neoplastic transformation1-3. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets from two intestinal damage models4,5 and using pharmacological, transcriptomics and genetic tools, we identified liver X receptor (LXR) pathway activation as a tissue adaptation to damage that reciprocally regulates intestinal regeneration and tumorigenesis. Using single-cell RNA sequencing, intestinal organoids, and gain- and loss-of-function experiments, we demonstrate that LXR activation in intestinal epithelial cells induces amphiregulin (Areg), enhancing regenerative responses. This response is coordinated by the LXR-ligand-producing enzyme CYP27A1, which was upregulated in damaged intestinal crypt niches. Deletion of Cyp27a1 impaired intestinal regeneration, which was rescued by exogenous LXR agonists. Notably, in tumour models, Cyp27a1 deficiency led to increased tumour growth, whereas LXR activation elicited anti-tumour responses dependent on adaptive immunity. Consistently, human colorectal cancer specimens exhibited reduced levels of CYP27A1, LXR target genes, and B and CD8 T cell gene signatures. We therefore identify an epithelial adaptation mechanism to damage, whereby LXR functions as a rheostat, promoting tissue repair while limiting tumorigenesis.

Intestinal stem cells (ISCs) are the regenerative force of the gut epithelium. Lgr5+-ISC have been shown to respond to changes in their microenvironment by coping with different metabolites, adapting to caloric changes, and recovering from injury and inflammation. However, how pathogenic bacteria affect adult stem cell regeneration and, as a consequence, the overall tissue adaption to infection has yet to be explored in depth. Here, we interrogated early Lgr5+ ISC responses to an enteric intracellular pathogen by profiling individual IECs from the mouse small intestine. Utilizing GFP-labeled Salmonella enterica, we isolated intracellular invaded cells to elucidate invasion programs of epithelial cell subsets. In particular, we identified a Salmonella -specific infection signature comprised of antimicrobial peptide (AMP) genes, including the Defensin gene family. Our findings demonstrate that Salmonella enterica targets differentiated Paneth, enterocytes, and stem/progenitor cells at these early stages of infection. In response, a rapid Lg5+ ISC-driven cellular remodeling to enterocyte and Paneth lineages expressing AMP genes is initiated to combat the intruders. Importantly, we uncovered an ISC differentiation program via inflammasome activation to protect the crypt environment, while eliminating infected stem cells from the overall stem cell pool. This novel Lgr5+ stem cell defense mechanism not only protects the gut epithelium from persistent bacterial infection but also promotes tissue regeneration. We propose epithelial remodeling to AMP-secreting cells as a novel innate immune response to handle different gut stresses mediated by Lgr5+ ISCs to maintain organizational principles of gut homeostasis and physiology. ### Competing Interest Statement The authors have declared no competing interest.

Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens1, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways are unclear2. Here we define nasal glandular acinar structures and the turbinates as immunological niches that recruit IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALTs)3. Using intact organ imaging, we demonstrate that nasal vaccination induces B cell expansion in the subepithelial dome of the NALT, followed by invasion into commensal-bacteria-driven chronic germinal centres in a T cell-dependent manner. Initiation of the germinal centre response in the NALT requires pre-expansion of antigen-specific T cells, which interact with cognate B cells in interfollicular regions. NALT ablation and blockade of PSGL-1, which mediates interactions with endothelial cell selectins, demonstrated that NALT-derived IgA-expressing B cells home to the turbinate region through the circulation, where they are positioned primarily around glandular acinar structures. CCL28 expression was increased in the turbinates in response to vaccination and promoted homing of IgA+ B cells to this site. Thus, in response to nasal vaccination, the glandular acini and turbinates provide immunological niches that host NALT-derived IgA-secreting cells. These cellular events could be manipulated in vaccine design or in the treatment of upper airway allergic responses. Nasal vaccination induces B cell expansion in the nasal-associated lymphoid tissues, followed by homing to the nasal turbinates and glandular acinar structures.

The enteric nervous system (ENS) senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions, in health and disease. However, mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging and existing research methods limit experimental controllability and throughput. Here, we present a novel optogenetics-integrated gut organ culture system that enables real-time, whole-tissue stimulation of specific ENS lineages, allowing for detailed analysis of their functional impact. We demonstrate that optogenetic activation of enteric cholinergic neurons rapidly modulates intestinal physiology. Interestingly, distinct neuronal firing patterns differentially modulate neuro-immunological gene expression and epithelial barrier integrity. Furthermore, diverse enteric neuronal lineages exert distinct regulatory roles. While cholinergic activation promotes gene-sets associated with type-2 immunity, tachykininergic enteric neurons differentially control mucosal defense programs. Remarkably, luminal introduction of the immunomodulatory bacterium C. ramosum significantly remodeled cholinergic-induced neuro-immunological transcription. These findings suggest that complex combinatorial signals delivered by gut microbes and enteric neurons are locally integrated to fine-tune intestinal immunity and barrier defense. Collectively, we provide a powerful platform for systematic discovery and mechanistic exploration of functional neuroimmune connections, and their potential modulation by drugs, microbes, or metabolites. Short abstract The enteric nervous system senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions. Mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging. We developed an optogenetics-integrated gut organ culture system for real-time neuronal stimulation and analysis. We revealed neuronal-specific activity patterns, which differentially regulate intestinal transcription and epithelial barrier integrity. Collectively, we provide a powerful platform to test neuroimmune connections and their potential modulation by drugs, microbes, or metabolites. ### Competing Interest Statement The authors have declared no competing interest.

Legend for Supplementary Figures S1-S8.

5FU and CPT11 display opposite effects on β-catenin localization in CRC colons (S1); 5FU and CPT11 display opposite effects on MDSC accumulation and CD247 expression in the colons of CRC-mice (S2); 5FU or CPT11 chemotherapies do not alter the elevated Treg levels in spleens from CRC-mice (S3); A combined 5FU and CPT11 therapy preserves immunosuppression (S4); A schematic representation of mouse model for CRC in which MDSCs were in vivo depleted in CPT11 treated mice by Gr1 mAb administration every 3 days (S5); 5FU and CPT11 differently affect monocytic/granulocytic MDSC sensitivity to apoptosis (S6); 5FU and CPT11 treatments display opposite effects on mRNA expression levels of pro-inflammatory molecules (S7); 5FU and CPT11 treatments differently affect the immunological profile of mice exhibiting a pathology free chronic inflammation (S8).

Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways remain unknown. Here, we define glandular acinus structures of the nasal turbinates as an immunological niche that recruits IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALT) in response to intranasal vaccination. Using intact organ imaging to visualize cognate T and B cells in the upper airways, we demonstrate that nasal vaccination induced extensive B cell expansion in the subepithelial dome (SED) of the NALT, followed by invasion into commensal bacteria-driven chronic germinal centers (GCs) in a T cell-dependent manner. Antigen-specific B cell response in the NALT required pre-expansion of cognate T cells, which initiate the immune response in the inter-follicular regions of the NALT, and occurred effectively in the presence of Monophosphoryl-Lipid A (MPLA), a synthetic, non-toxic TLR-4 agonist. NALT ablation and blockade of PSGL-1 demonstrated that intranasal vaccination generates IgA-expressing plasma cells that home to the nasal turbinates through the blood circulation where they are positioned primarily around glandular acinus structures. Thus, the glandular part of the nasal turbinate is an immunological niche that hosts NALT-derived IgA-secreting cells. These cellular events can be manipulated to design vaccines against inhaled pathogens or in the treatment of upper airway allergic responses.

Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene–trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene–trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox. Polygenic Priority Score (PoPS) prioritizes candidate effector genes at complex trait loci by integrating genome-wide association summary statistics with other data types. Combining PoPS with methods that leverage local genetic signals further improves the performance.

Lymphocyte priming in lymph nodes (LNs) was postulated to depend on the formation of stable T cell receptor (TCR)-specific immune synapses (ISs) with antigen (Ag)-presenting dendritic cells (DCs). The high-affinity LFA-1 ligand ICAM-1 was implicated in different ISs studied in vitro. We dissect the in vivo roles of endogenous DC ICAM-1 in Ag-stimulated T cell proliferation and differentiation and find that under type 1 polarizing conditions in vaccinated or vaccinia virus-infected skin-draining LNs, Ag-presenting DCs engage in ICAM-1-dependent stable conjugates with a subset of Ag-specific CD8 blasts. Nevertheless, in the absence of these conjugates, CD8 lymphocyte proliferation and differentiation into functional cytotoxic T cells (CTLs) and skin homing effector lymphocytes takes place normally. Our results suggest that although CD8 T cell blasts engage in tight ICAM-1-dependent DC-T ISs, firm ISs are dispensable for TCR-triggered proliferation and differentiation into productive effector lymphocytes.

Primers for quantitative Real Time PCR.