Expansion in CD39+ CD4+ Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

Htlv-1 infection is associated with several inflammatory disorders,including the neurodegenerative condition htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). it is unclear why a minority of infected subjects develops ham/tsp. cd4+ t cells are the main target of infection and play a pivotal role in regulating immunity to htlv and are hypothesized to participate in the pathogenesis of ham/tsp. the cd39 ectonucleotidase receptor is expressed on cd4+ t cells and based on co-expression with cd25,marks t cells with distinct regulatory (cd39+cd25+) and effector (cd39+cd25-) function. here,we investigated the expression of cd39 on cd4+ t cells from a cohort of ham/tsp patients,htlv-1 asymptomatic carriers (ac),and matched uninfected controls. the frequency of cd39+ cd4+ t cells was increased in htlv-1 infected patients,regardless of clinical status. more importantly,the proportion of the immunostimulatory cd39+cd25- cd4+ t-cell subset was significantly elevated in ham/tsp patients as compared to ac and phenotypically had lower levels of the immunoinhibitory receptor,pd-1. we saw no difference in the frequency of cd39+cd25+ regulatory (treg) cells between ac and ham/tsp patients. however,these cells transition from being anergic to displaying a polyfunctional cytokine response following htlv-1 infection. cd39-cd25+ t cell subsets predominantly secreted the inflammatory cytokine il-17. we found that ham/tsp patients had significantly fewer numbers of il-17 secreting cd4+ t cells compared to uninfected controls. taken together,we show that the expression of cd39 is upregulated on cd4+ t cells ham/tsp patients. this upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different cd39 t cell subsets. cd39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of ham/tsp. © 2013 leal et al.