High Expression of CD244 and SAP Regulated CD8+ T Cell Responses of Patients with HTLV-I Associated Neurologic Disease

PLoS Pathogens

Steven Jacobson¹  Unsong Oh¹  Yoshimi Enose-Akahata¹  Eiji Matsuura¹ 

[1] Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: T cells;    Cytotoxic T cells;    Cell degranulation;    Small interfering RNAs;    T cell receptors;    NK cells;    CD coreceptors;    Inflammatory diseases;   

DOI  :  10.1371/journal.ppat.1000682

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

HTLV-I-specific CD8+ T cells have been characterized with high frequencies in peripheral blood and cerebrospinal fluid and production of proinflammatory cytokines, which contribute to central nervous system inflammation in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, little is known about the differences in CD8+ T cell activation status between asymptomatic carrier (ACs) and patients with HAM/TSP. The expression of CD244, a signaling lymphocyte activation molecule (SLAM) family receptor, was significantly higher on CD8+ T cells in HTLV-I-infected patients, both ACs and patients with HAM/TSP, than those on healthy normal donors (NDs). Blockade of CD244 inhibited degranulation and IFN-γ production in CD8+ T cells of patients with HAM/TSP, suggesting that CD244 is associated with effector functions of CD8+ T cells in patients with HAM/TSP. Moreover, SLAM-associated protein (SAP) was overexpressed in patients with HAM/TSP compared to ACs and NDs. SAP expression in Tax-specific CTLs was correlated in the HTLV-I proviral DNA loads and the frequency of the cells in HTLV-I-infected patients. SAP knockdown by siRNA also inhibited IFN-γ production in CD8+ T cells of patients with HAM/TSP. Thus, the CD244/SAP pathway was involved in the active regulation of CD8+ T cells of patients with HAM/TSP, and may play roles in promoting inflammatory neurological disease.

【 授权许可】

CC BY