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Transport Of Ldl-Derived Cholesterol From The Npc1 Compartment To The Er Involves The Trans-Golgi Network And The Snare Protein Complex, Yasuomi Urano, Hiroshi Watanabe, Stephanie R. Murphy, Yohei Shibuya, Yong Geng, Andrew Peden, Catherine Chang, Ta Yuan Chang

Dartmouth Scholarship

Mammalian cells acquire cholesterol mainly from LDL. LDL enter the endosomes, allowing cholesteryl esters to be hydrolyzed by acid lipase. The hydrolyzed cholesterol (LDL-CHOL) enters the Niemann-Pick type C1 (NPC1)-containing endosomal compartment en route to various destinations. Whether the Golgi is involved in LDL-CHOL transport downstream of the NPC1 compartment has not been demonstrated. Using subcellular fractionation and immunoadsorption to enrich for specific membrane fractions, here we show that, when parental Chinese hamster ovary (CHO) cells are briefly exposed to (3)H-cholesteryl linoleate (CL) labeled-LDL, newly liberated (3)H-LDL-CHOL appears in membranes rich in trans-Golgi network (TGN) long before it becomes available …

Viral Vectors In The Research Laboratory: Just How Safe Are They?, Dawn P. Wooley, Kimberly Kay Morris, Robert Mcrae, John C. Trefry

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung

Dartmouth Scholarship

MgrA is a pleiotropic regulator that controls autolysis, virulence, and efflux pump activity in Staphylococcus aureus. We recently found that mgrA mutants of strains RN6390, SH1000, and MW2 also displayed enhanced biofilm formation compared with their respective parents. The biofilms formed by mgrA mutants of RN6390 and MW2 are independent of sigB and ica loci, two genetic elements that have been previously associated with biofilm formation in S. aureus. Biofilms formed by mgrA mutants are dependent on the expression of surface proteins mediated by the sortase gene srtA. Extracellular DNA was also a crucial component of the early biofilm of …

Ovarian Cancer: Emerging Concept On Cancer Stem Cells., Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cells. Recent studies have shown that ovarian cancer also contains stem cells or tumor-initiating cells. Moreover, ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions to select for self-renewing, …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Biochemistry and Microbiology

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood.

RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Factors Contributing To The Biofilm-Deficient Phenotype Of Staphylococcus Aureus Sara Mutants, Laura H. Tsang, James E. Cassat, Lindsey N. Shaw, Karen E. Beenken, Mark S. Smeltzer

Molecular Biosciences Faculty Publications

Mutation of sarA in Staphylococcus aureus results in a reduced capacity to form a biofilm, but the mechanistic basis for this remains unknown. Previous transcriptional profiling experiments identified a number of genes that are differentially expressed both in a biofilm and in a sarA mutant. This included genes involved in acid tolerance and the production of nucleolytic and proteolytic exoenzymes. Based on this we generated mutations in alsSD, nuc and sspA in the S. aureus clinical isolate UAMS-1 and its isogenic sarA mutant and assessed the impact on biofilm formation. Because expression of alsSD was increased in a biofilm but …

The Untapped Power Of "We Don't Know": Epistemological Humility In The Era Of Covid-19, Diasinou Fioravante, Rong-Yu Liu, John H. Byrne

Faculty, Staff and Student Publications

The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated …

Gender Differences In Motivation To Resolve Eating And Body Image Concerns In College Students, Harold L. Merriman, C. Jayne Brahler, Laura Dinan, Lauren Finzer

Physical Therapy Faculty Publications

The objective of this study was to identify similarities and differences between college women and men with respect to their eating and body image concerns, weight fluctuation and level of motivation to resolve these concerns. 101 University of Dayton students participated in this study. Students completed an eating and body concern survey online.

Body image concerns were significantly greater for females compared to males (p=0.007) and significantly greater as motivation level to resolve the concerns increased (p=0.019). Eating concerns followed the same trends but did not reach statistical significance. Weight fluctuation in both genders increased significantly as motivation level increased …

Immune Evasion By Rabies Viruses Through The Maintenance Of Blood-Brain Barrier Integrity., Anirban Roy, Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The attenuated rabies virus (RV) strain Challenge Virus Standard (CVS)-F3 and a highly pathogenic strain associated with the silver-haired bats (SHBRV) can both be cleared from the central nervous system (CNS) tissues by appropriate antiviral immune mechanisms if the effectors are provided access across the blood-brain barrier (BBB). In the case of SHBRV infection, antiviral immunity develops normally in the periphery but fails to open the BBB, generally resulting in a lethal outcome. To determine whether or not an absence in the CNS targeted immune response is associated with the infection with other pathogenic RV strains, we have assessed the …

Molecular Processes That Handle — And Mishandle — Dietary Lipids, Kevin Jon Williams

Department of Medicine Faculty Papers

Overconsumption of lipid-rich diets, in conjunction with physical inactivity, disables and kills staggering numbers of people worldwide. Recent advances in our molecular understanding of cholesterol and triglyceride transport from the small intestine to the rest of the body provide a detailed picture of the fed/fasted and active/sedentary states. Key surprises include the unexpected nature of many pivotal molecular mediators, as well as their dysregulation — but possible reversibility — in obesity, diabetes, inactivity, and related conditions. These mechanistic insights provide new opportunities to correct dyslipoproteinemia, accelerated atherosclerosis, insulin resistance, and other deadly sequelae of overnutrition and underexertion.

Intraretinal Signaling By Ganglion Cell Photoreceptors To Dopaminergic Amacrine Neurons, Dao-Qi Zhang, Kwoon Y. Wong, Patricia J. Sollars, David M. Berson, Gary E. Pickard, Douglas G. Mcmahon

School of Veterinary and Biomedical Sciences: Faculty Publications

Retinal dopaminergic amacrine neurons (DA neurons) play a central role in reconfiguring retinal function according to prevailing illumination conditions, yet the mechanisms by which light regulates their activity are poorly understood. We investigated the means by which sustained light responses are evoked in DA neurons. Sustained light responses were driven by cationic currents and persisted in vitro and in vivo in the presence of L-AP4, a blocker of retinal ON-bipolar cells. Several characteristics of these L-AP4-resistant light responses suggested that they were driven by melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), including long latencies, marked poststimulus persistence, and a peak …

Deregulation Of Muc4 In Gastric Adenocarcinoma: Potential Pathobiological Implication In Poorly Differentiated Non-Signet Ring Cell Type Gastric Cancer., S. Senapati, P. Chaturvedi, P. Sharma, G Venkatraman, Jane L. Meza, W. El-Rifai, H. K. Roy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n = 45) and gastric adenocarcinoma (n = 83; P < 0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P < 0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein.

Emerging Issues In Forensic Dna Profiling: Databases And Advisory Boards, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Intravenous Inoculation Of Silver-Haired Bat Rabies Virus, But Not Of A Canine Strain, Elicits Lethal Encephalophathy In Mice By Fast Brain Invasion Via Neurosecretory Hypothalamic Fibers, Mirjam Ar Preuss, Marie-Luise Faber, Gene S. Tan, Bernhard Dietzschold, Matthias J. Schnell, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons

Dartmouth Scholarship

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF …

Presence Of Endometrial Adenocarcinoma In Situ In Complex Atypical Endometrial Hyperplasia Is Associated With Increased Incidence Of Endometrial Carcinoma In Subsequent Hysterectomy., Khush Mittal, Matjaz Sebenik, Cybil Irwin, Zhijije Yan, Dorota Popiolek, John Curtin, Juan Palazzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The distinction of complex atypical endometrial hyperplasia from endometrial adenocarcinoma is often problematic. Foci of back-to-back arrangement of glands or foci of cribriform arrangement of glands smaller than 2.1 mm in diameter are considered insufficient for the diagnosis of endometrial adenocarcinoma by some authors, and sufficient to be diagnosed as endometrial adenocarcinoma by other authors. We refer to these foci as endometrial adenocarcinoma in situ. In this study, we evaluated findings in subsequent hysterectomy in complex atypical endometrial hyperplasia patients with and without adenocarcinoma in situ. Follow-up findings, including the presence or absence of endometrial adenocarcinoma in the hysterectomy specimen, …

Neurovirulence Of Polytropic Murine Retrovirus Is Influenced By Two Separate Regions On Opposite Sides Of The Envelope Protein Receptor Binding Domain, Karin E. Peterson, Susan Pourciau, Min Du, Rachel Lacasse, Melissa Pathmajeyan, David J. Poulsen, Mavis Agbandje-Mckenna, Kathy Wehrly, Bruce Chesebro

Biomedical and Pharmaceutical Sciences Faculty Publications

Changes in the envelope proteins of retroviruses can alter the ability of these viruses to infect the central nervous system (CNS) and induce neurological disease. In the present study, nine envelope residues were found to influence neurovirulence of the Friend murine polytropic retrovirus Fr98. When projected on a three-dimensional model, these residues were clustered in two spatially separated groups, one in variable region B of the receptor binding site and the other on the opposite side of the envelope. Further studies indicated a role for these residues in virus replication in the CNS, although the residues did not affect viral …

Overexpression Of Matrix Metalloproteinase 9 In Tumor Epithelial Cells Correlates With Colorectal Cancer Metastasis., David S Zuzga, Ahmara Vivian Gibbons, Peng Li, Wilhelm Johannes Lubbe, Inna Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancer mortality largely reflects metastasis, the spread of the disease to distant organs. Matrix metalloproteinase 9 (MMP-9) is a key regulator of metastasis and a target for anticancer strategies in colon cancer. Here, the overexpression of MMP-9 in pure tumor epithelial, but nor stromal, cell populations was associated with metastatic progression of colorectal cancer, as defined by reverse transcriptase-polymerase chain reaction (qRT-PCR) and confirmed by immunostaining. Thus, cancer cell MMP-9 represents a novel, selective prognostic and predictive factor that may be exploited for more effective disease stage stratification and therapeutic regimen selection in patients with colorectal cancer.

Β-Funaltrexamine Inhibits Inducible Nitric-Oxide Synthase Expression In Human Astroglial Cells, Randall L. Davis, Daniel J. Buck, Neda Saffarian, Shekhar Mohan, Udaya Desilva, Samodha C. Fernando, Craig W. Stevens

Samodha C. Fernando Publications

The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon γ, tumor necrosis factor α, and interleukin-1β, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, β-funaltrexamine (β-FNA), on cytokine induced iNOS expression in human astroglia. β-FNA dose-dependently …

Shifts In Southern Wisconsin Forest Canopy And Understory Richness, Composition, And Heterogeneity, David A. Rogers, Thomas P. Rooney, Daniel Olson, Donald M. Waller

Biological Sciences Faculty Publications

We resurveyed the under- and overstory species composition of 94 upland forest stands in southern Wisconsin in 2002–2004 to assess shifts in canopy and understory richness, composition, and heterogeneity relative to the original surveys in 1949–1950. The canopy has shifted from mostly oaks (Quercus spp.) toward more mesic and shade-tolerant trees (primarily Acer spp.). Oak-dominated early-successional stands and those on coarse, nutrient-poor soils changed the most in canopy composition. Understories at most sites (80%) lost native species, with mean species density declining 25% at the 1-m² scale and 23.1% at the 20-m² scale. Woody species have increased …

A Review Of Physiological Simulation Models Of Intracranial Pressure Dynamics, Wayne W. Wakeland, Brahm Goldstein

Complex Systems Faculty Publications and Presentations

This paper reviews the literature regarding the development, testing, and application of physiology-based computer simulation models of intracranial pressure dynamics. Detailed comparative information is provided in tabular format about the model variables and logic, any data collected, model testing and validation methods, and model results. Several syntheses are given that summarize the research carried out by influential research teams and researchers, review important findings, and discuss the methods employed, limitations, and opportunities for further research.

A Functional Collagen Adhesin Gene, Acm, In Clinical Isolates Of Enterococcus Faecium Correlates With The Recent Success Of This Emerging Nosocomial Pathogen, Sreedhar R Nallapareddy, Kavindra V Singh, Pablo C Okhuysen, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm(+)) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P

Contribution Of The Collagen Adhesin Acm To Pathogenesis Of Enterococcus Faecium In Experimental Endocarditis, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Deltaacm::cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations (P < 0.0001) and for valve colonization 1 and 3 hours after infection (P or=50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.

Domain-Oriented Reduction Of Rule-Based Network Models, Nikolay M. Borisov, Alexander S. Chistopolsky, James R. Faeder, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The coupling of membrane-bound receptors to transcriptional regulators and other effector functions is mediated by multi-domain proteins that form complex assemblies. The modularity of protein interactions lends itself to a rule-based description, in which species and reactions are generated by rules that encode the necessary context for an interaction to occur, but also can produce a combinatorial explosion in the number of chemical species that make up the signaling network. We have shown previously that exact network reduction can be achieved using hierarchical control relationships between sites/domains on proteins to dissect multi-domain proteins into sets of non-interacting sites, allowing the …

Accelerated High Fidelity Prion Amplification Within And Across Prion Species Barriers, Kristi M. Green, Joaquín Castilla, Tanya S. Seward, Dana L. Napier, Jean E. Jewell, Claudio Soto, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier …

Mitochondrial Redox Signaling By P66shc Is Involved In Regulating Androgenic Growth Stimulation Of Human Prostate Cancer Cells., Suresh Veeramani, Ta-Chun Yuan, Fen-Fen Lin, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5alpha-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect …

A Cyclin D1/Microrna 17/20 Regulatory Feedback Loop In Control Of Breast Cancer Cell Proliferation., Zuoren Yu, Chenguang Wang, Min Wang, Zhiping Li, Mathew C Casimiro, Manran Liu, Kongming Wu, James Whittle, Xiaoming Ju, Terry Hyslop, Peter Mccue, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3' untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1-deficient breast cancer cells. Mammary epithelial cell-targeted cyclin D1 expression induced miR-17-5p and miR-20a expression …

Muc4 Activates Her2 Signalling And Enhances The Motility Of Human Ovarian Cancer Cells., Moorthy P. Ponnusamy, A. P. Singh, Maneesh Jain, S. Chakraborty, N. Moniaux, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

The mucin MUC4 is a high molecular weight transmembrane glycoprotein. It consists of a mucin-type subunit (MUC4alpha) and a transmembrane growth factor-like subunit (MUC4beta). The mucin MUC4 is overexpressed in many epithelial malignancies including ovarian cancer, suggesting a possible role in the pathogenesis of these cancers. In this study, we investigated the functional role of MUC4 in the human ovarian cancer cell line SKOV3. The mucin MUC4 was ectopically expressed by stable transfection, and its expression was examined by western blot and confocal microscopy analyses. The in vitro studies demonstrated an enhanced motility of MUC4-expressing SKOV3 cells compared with the …

Population Structure Of Limenitis Butterflies In Hickman, Kentucky, Mollie Johnson

Masters Theses & Specialist Projects

Two species of Limenitis butterflies occur along the Mississippi River at Hickman, Kentucky: the viceroy, L. archippus, and the red-spotted purple, L. arthemis astyanax. Limenitis archippus occurs at a frequency that is 10-30 times more abundant than its congener, L. arthemis astyanax. Interspecific matings between L. archippus and L. arthemis astyanax are very rare in the wild and give rise to a hybrid form Limenitis archippus X L. arthemis astyanax form rubidus. Only 7 heterospecific pairings between the parental species and 72 "rubidus" individuals have been documented in the wild in all of North America. Of these documented cases, 2 …

Distinct Functions Of Autoreactive Memory And Effector Cd4+ T Cells In Experimental Autoimmune Encephalomyelitis, Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury

Jay Reddy Publications

The persistence of human autoimmune diseases is thought to be mediated predominantly by memory T cells. We investigated the phenotype and migration of memory versus effector T cells in vivo in experimental autoimmune encephalomyelitis (EAE). We found that memory CD4⁺ T cells up-regulated the activation marker CD44 as well as CXCR3 and ICOS, proliferated more and produced more interferon-γ and less interleukin-17 compared to effector T cells. Moreover, adoptive transfer of memory T cells into T cell receptor (TCR)αβ^-/- recipients induced more severe disease than did effector CD4⁺ T cells with marked central nervous system inflammation and …