T-cell development requires cytokines and intimate contact with stromal cells provided exclusively by the thymus. Consequently, an in vitro model of thymocyte differentiation, fetal thymic organ culture (FTOC), has been developed. FTOC recapitulates the normal development of T-cells derived from both mouse and human progenitor populations, providing a more rapid means to study T-cell development compared with alternative in vivo approaches. Furthermore, FTOC is easily amenable to genetic manipulation using retroviral gene transfer. In this chapter, we outline the basic FTOC technique and describe several applications, including retroviral transduction of mouse thymocyte subsets and human CD34+ stem/progenitor cells.
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http://dx.doi.org/10.1385/1-59259-826-9:311 | DOI Listing |
Int J Mol Sci
January 2025
State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.
View Article and Find Full Text PDFSci Signal
January 2025
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
Activation of the stimulator of interferon genes (STING) pathway by cytosolic DNA leads to the activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB). Although many viruses produce proteins that inhibit IRF3-dependent antiviral responses, some viruses produce proteins that inhibit STING-induced NF-κB activation without blocking IRF3 activation. Here, we found that STING-activated, NF-κB-dependent, and IRF3-independent innate immunity inhibited the replication of the DNA virus herpes simplex virus type 1 (HSV-1), the RNA virus coxsackievirus A16 (CV-A16), and the retrovirus HIV-1.
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia.
View Article and Find Full Text PDFMethods Cell Biol
January 2025
Division of Clinical Pharmacology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and LMU University Hospital, Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany. Electronic address:
Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Swiss Institute of Bioinformatics, Lausanne, Switzerland
Background: The adoptive cell transfer (ACT) of T cell receptor (TCR)-engineered T cells targeting the HLA-A2-restricted epitope NY-ESO-1 (A2/NY) has yielded important clinical responses against several cancers. A variety of approaches are being taken to augment tumor control by ACT including TCR affinity-optimization and T-cell coengineering strategies to address the suppressive tumor microenvironment (TME). Most TCRs of clinical interest are evaluated in immunocompromised mice to enable human T-cell engraftment and do not recapitulate the dynamic interplay that occurs with endogenous immunity in a treated patient.
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