In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-23)
Abstract:
Human T-lymphotropic virus 1 (HTLV-1) infection causes two serious diseases: adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Immunological studies have revealed that HTLV-1 Tax-specific CD8 + cytotoxic T-cells (Tax-CTLs) in asymptomatic carriers (ACs) and ATL patients play an important role in the elimination of HTLV-1-infected host cells, whereas Tax-CTLs in HAM patients trigger an excessive immune response against HTLV-1-infected host cells infiltrating the central nervous system (CNS), leading to local inflammation. Our previous evaluation of HTLV-1 Tax 301-309 (SFHSLHLLF)-specific Tax-CTLs (Tax 301-309 -CTLs) revealed that a unique T-cell receptor (TCR) containing amino acid (AA)-sequence motif PDR, was shared among HLA-A*24:02 + ACs and ATL patients and behaved as an eliminator by strong activity against HTLV-1. However, it remains unclear whether PDR + Tax 301-309 -CTLs also exist in HLA-A*24:02 + HAM patients and are involved in the pathogenesis of HAM. In the present study, by high-throughput TCR repertoire analysis technology, we revealed TCR repertoires of Tax 301-309 -CTLs in peripheral blood (PB) of HLA-A*24:02 + HAM patients were skewed, and a unique TCR-motif PDR was conserved in HAM patients (10 of 11 cases). The remaining case dominantly expressed (-DR, P-R, and PD-), which differed by one AA from PDR. Overall, TCRs with unique AA-sequence motifs PDR, or (-DR, P-R, and PD-) accounted for a total of 0.3-98.1% of Tax 301-309 -CTLs repertoires of HLA-A*24:02 + HAM patients. Moreover, TCR repertoire analysis of T-cells in the cerebrospinal fluid (CSF) from four HAM patients demonstrated the possibility that PDR + Tax 301-309 -CTLs and (-DR, P-R, and PD-) + Tax 301-309 -CTLs efficiently migrated and accumulated in the CSF of HAM patients fostering increased inflammation, although we observed no clear significant correlation between the frequencies of them in PB and the levels of CSF neopterin, a known disease activity biomarker of HAM. Furthermore, to better understand the potential function of PDR + Tax 301-309 -CTLs, we performed immune profiling by single-cell RNA-sequencing of Tax 301-309 -CTLs, and the result showed that PDR + Tax 301-309 -CTLs up-regulated the gene expression of natural killer cell marker KLRB1 (CD161), which may be associated with T-cell activation and highly cytotoxic potential of memory T-cells. These findings indicated that unique and shared PDR + Tax 301-309 -CTLs have a potential role in promoting local inflammation within the CNS of HAM patients.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.993025
DOI:
10.3389/fimmu.2022.993025.s001
DOI:
10.3389/fimmu.2022.993025.s002
DOI:
10.3389/fimmu.2022.993025.s003
DOI:
10.3389/fimmu.2022.993025.s004
DOI:
10.3389/fimmu.2022.993025.s005
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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