HTLV-1-Specific CTL Accumulation in CSF Contributes to Neuroinflammation in HTLV-1-Associated Myelopathy

Area of Science:

• Neuroimmunology
• Virology
• Neurology

Background:

• Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological disorder characterized by chronic central nervous system (CNS) inflammation.
• HTLV-1-specific cytotoxic CD8+ T lymphocytes (CTLs) are implicated in HAM/TSP pathogenesis, but their dynamics within the CNS are not fully understood.

Purpose of the Study:

• To investigate the accumulation of HTLV-1-specific CTLs in the cerebrospinal fluid (CSF) of HAM/TSP patients.
• To evaluate the association between HTLV-1-specific CTLs in the CSF and markers of neuroinflammation and neural damage.

Main Methods:

• Comparison of HTLV-1-specific CTL frequencies in paired peripheral blood (PB) and CSF from HAM/TSP patients and asymptomatic HTLV-1 carriers (ACs) using MHC/antigen tetramers.
• Analysis of cytokine levels and neurofilament light chain (NfL) concentration in the CSF of both groups.

Main Results:

• Significantly higher frequencies of HTLV-1-specific CTLs were observed in the PB and, more pronouncedly, in the CSF of HAM/TSP patients compared to ACs.
• HTLV-1-specific CTLs selectively accumulated in the CSF of HAM/TSP patients, unlike cytomegalovirus-specific CTLs.
• CSF CTL frequency correlated positively with cytokine levels, and CSF NfL levels were elevated in HAM/TSP patients, correlating with HTLV-1 proviral load.

Conclusions:

• HTLV-1-specific CTLs selectively accumulate in the CSF of HAM/TSP patients.
• This accumulation, along with proliferating HTLV-1-infected cells, likely drives chronic inflammation and contributes to neural damage in HAM/TSP.