# In Vitro Model of the Human Blood–Brain Barrier to Explore HTLV-1 Immunopathogenesis

## TL;DR

This study uses a lab model of the blood-brain barrier to investigate how HTLV-1 infection leads to neurological disease.

## Contribution

A novel in vitro model is developed to explore HTLV-1 immunopathogenesis at the blood-brain barrier.

## Key findings

- HAM/TSP carriers showed higher cytokine production compared to HTLV-1-infected individuals without HAM/TSP.
- Increased neuronal death was observed in co-cultures mimicking HAM/TSP carriers.
- Mononuclear cell infiltration may contribute to neuronal damage in HAM/TSP.

## Abstract

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death.