We have used HSCA-2, an mAb that recognizes a sialic acid-dependent epitope on the low molecular mass (approximately 115-kDa) glycoform of CD43 that is expressed in resting T and NK cells, to examine the expression characteristics and stimulatory functions of CD43 in human CD4+ memory T cells. Having previously reported that the memory cells that respond to recall Ags in a CD4+ CD45RO+ T cell population almost all belong to a subset whose surface CD43 expression levels are elevated, we now find that exposing these same memory T cells to HSCA-2 mAb markedly increases their proliferative responsiveness to recall Ags. We think it unlikely that this increase in responsiveness is a result of CD43-mediated monocyte activation, especially given that the HSCA-2 mAb differs from all previously used CD43 mAbs in having no obvious binding specificity for monocyte CD43. Predictably, treatment with HSCA-2 mAb did not lead to significant recall responses in CD4+ CD45RO+ T cells, whose CD43 expression levels were similar to or lower than those of naive cells. Other experiments indicated that the HSCA-2 mAb was capable of enhancing the proliferative responsiveness of CD4+ memory T cells that had been exposed to polyclonal stimulation by monocyte-bound CD3 mAb and could also act in synergy with CD28 mAb to enhance the responsiveness of CD4+ T cells to CD3 stimulation. Taken together, these findings suggest that the CD43 molecules expressed on CD4+ memory T cells may be capable of enhancing the costimulatory signaling and hence providing accessory functions to TCR-mediated activation processes.
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http://dx.doi.org/10.4049/jimmunol.172.12.7246 | DOI Listing |
Appl Biochem Biotechnol
January 2025
The Joint Institute of Tobacco and Health, No. 367, Honglin Road, Kunming, 650231, China.
Epidemiologic study suggests that nicotine reduces the risk of Parkinson's disease (PD) and thus could serve as a potential treatment. In this study, we aimed to investigate the effect of nicotine on the behavioral phenotypes and pathological characteristics of mice induced by human alpha-synuclein preformed fibers (α-syn-PFF). Mice were injected with 5 µg of human α-syn-PFF in the hippocampus while administering nicotine-containing drinking water (200 µg/mL).
View Article and Find Full Text PDFCommun Biol
January 2025
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, China.
The retrosplenial cortex (RSP) is a complex brain region with multiple interconnected subregions that plays crucial roles in various cognitive functions, including memory, spatial navigation, and emotion. Understanding the afferent and efferent connectivity of the RSP is essential for comprehending the underlying mechanisms of its functions. Here, via viral tracing and fluorescence micro-optical sectioning tomography (fMOST), we systematically investigated the anatomical organisation of the upstream and downstream circuits of glutamatergic and GABAergic neurons in the dorsal and ventral RSP.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061-0910, USA.
Sepsis is a leading cause of death worldwide, with most patient mortality stemming from lingering immunosuppression in sepsis survivors. This is due in part to immune dysfunction resulting from monocyte exhaustion, a phenotype of reduced antigen presentation, altered CD14/CD16 inflammatory subtypes, and disrupted cytokine production. Whereas previous research demonstrated improved sepsis survival in Ticam2 mice, the contribution of TICAM2 to long-term exhaustion memory remained unknown.
View Article and Find Full Text PDFNature
January 2025
Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China.
Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers. T cells participate in a wide range of inflammatory diseases such as psoriasis, Crohn's disease, oesophagitis and multiple sclerosis, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Background: Alzheimer's disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neuronal circuits in AD, precluding precise targeting of E-I imbalance in AD treatment.
Method: In this work, we apply a Multiscale Neural Model Inversion (MNMI) framework to the resting-state functional MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify brain regions with disrupted E-I balance in a large network during AD progression.
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