Journal article
Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response
Viruses, v 16(9), 1443
10 Sep 2024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.
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Details
- Title
- Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response
- Creators
- Julie Joseph - Drexel UniversityThomas A. Premeaux - Cornell CollegeRitesh Tandon - Drexel UniversityEdward L. Murphy - University of California, San FranciscoRoberta Bruhn - VitalantChristophe Nicot - University of Kansas Medical CenterBobby Brooke Herrera - Rutgers, The State University of New JerseyAlexander Lemenze - Rutgers, The State University of New JerseyReem Alatrash - Rutgers, The State University of New JerseyPrince Baffour TontoLishomwa C. Ndhlovu - Cornell CollegePooja Jain - Drexel University
- Publication Details
- Viruses, v 16(9), 1443
- Publisher
- MDPI
- Number of pages
- 18
- Grant note
- NIH/NIMH: T32-MH079785
These studies are supported in part by the funding from NIH/NINDS via R01 NS097147 to P.J. J.J. was also supported by the Interdisciplinary and Translational Research Training Grant in NeuroAIDS, NIH/NIMH T32-MH079785.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine
- Web of Science ID
- WOS:001323603000001
- Scopus ID
- 2-s2.0-85205062712
- Other Identifier
- 991021903271804721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Virology