Dendritic cells (DCs) are considered to be the major APCs with potent activity for priming of naive CD4 and CD8 T cells. However, T cell priming can also be achieved by other APCs including macrophages, B cells, or even nonhematopoietic cell types. Systemic low-dose infection of mice with lymphocytic choriomeningitis virus (LCMV) results in massive expansion of virus-specific CD4 and CD8 T cells. To determine the role of DCs as APCs and source of type I IFNs in this infection model, we used ΔDC mice in which DCs are constitutively ablated because of expression of the diphtheria toxin α subunit within developing DCs. ΔDC mice showed lower serum concentrations of IFN-β and IL-12p40, but normal IFN-α levels during the first days postinfection. No differences were found for proliferation of transferred TCR-transgenic cells during the early phase of infection, suggesting that T cell priming occurred with the same efficiency in wild-type and ΔDC mice. Expansion and cytokine expression of endogenous LCMV-specific T cells was comparable between wild-type and ΔDC mice during primary infection and upon rechallenge of memory mice. In both strains of infected mice the viral load was reduced below the limit of detection with the same kinetic. Further, germinal center formation and LCMV-specific Ab responses were not impaired in ΔDC mice. This indicates that DCs are dispensable as APCs for protective immunity against LCMV infection.
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http://dx.doi.org/10.4049/jimmunol.1502582 | DOI Listing |
Ecotoxicol Environ Saf
January 2025
College of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, China. Electronic address:
The T-2 toxin is a frequent contaminant in the global environment and agricultural production. Existing evidence suggests that the ingested T-2 toxin can enter the brain and exhibit neurotoxicity. However, it is still unknown whether T-2 toxin causes the depression-like behaviors.
View Article and Find Full Text PDFNeurobiol Dis
November 2024
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan. Electronic address:
The development of the nigrostriatal dopaminergic (DA) pathway in the brain involves many transcriptional and chemotactic molecules, and a deficiency of these molecules can cause nigrostriatal tract defects. However, the role of the end product, dopamine, in nigrostriatal pathway development has not been described. In the present study, we analyzed a mouse model of congenital dopamine and serotonin deficiency, namely, the aromatic l-amino acid decarboxylase (AADC) deficiency (Ddc) mouse model.
View Article and Find Full Text PDFBrain
October 2024
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, CA 92697, USA.
J Inherit Metab Dis
May 2024
Department of Biomedicine and Center for Translational Research in Parkinson's Disease, University of Bergen, Bergen, Norway.
Several mouse models have been developed to study human defects of primary and secondary inherited monoamine neurotransmitter disorders (iMND). As the field continues to expand, current defects in corresponding mouse models include enzymes and a molecular co-chaperone involved in monoamine synthesis and metabolism (PAH, TH, PITX3, AADC, DBH, MAOA, DNAJC6), tetrahydrobiopterin (BH) cofactor synthesis and recycling (adGTPCH1/DRD, arGTPCH1, PTPS, SR, DHPR), and vitamin B cofactor deficiency (ALDH7A1), as well as defective monoamine neurotransmitter packaging (VMAT1, VMAT2) and reuptake (DAT). No mouse models are available for human DNAJC12 co-chaperone and PNPO-B deficiencies, disorders associated with recessive variants that result in decreased stability and function of the aromatic amino acid hydroxylases and decreased neurotransmitter synthesis, respectively.
View Article and Find Full Text PDFInt J Mol Sci
November 2023
Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia.
The mammalian striatum is known to contain non-dopaminergic neurons that express dopamine (DA)-synthesizing enzymes and produce DA, responsible for the regulation of motor function. This study assessed the expression of DA-synthesizing enzymes in striatal neurons and their role in DA synthesis in transgenic mice expressing the green fluorescent protein (GFP) gene under the tyrosine hydroxylase (TH) gene promoter in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). We showed that, in Parkinsonian animals, the number of neurons expressing the TH gene increased by 1.
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