Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: Sao Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

National Institute of Allergy and Infectious Diseases (NIAID/NIH)[R37AI052731]

National Heart Lung and Blood Institute (NHLBI/NIH)[2R01-HL-62235]

AIDS Research Institute of University of California San Francisco

Brazilian Program for STD and AIDS

Ministry of Health[914/BRA/3014 -UNESCO/Kallas]

Sao Paulo City Health Department[2004-0.168.922-7/Kallas]

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/15856-9/Kallas]

John E. Fogarty International Center (FIRCA/NIH)[D43 TW00003]