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

Autor(es):Mostrar menos -

Leal, Fabio E. ^{[1, 2, 3]} ; Ndhlovu, Lishomwa C. ^{[1, 2]} ; Hasenkrug, Aaron M. ^[1] ; Bruno, Fernanda R. ^[4] ; Carvalho, Karina I. ^[4] ; Wynn-Williams, Harry ^[2] ; Neto, Walter K. ^{[5, 6]} ; Sanabani, Sabri S. ^[3] ; Segurado, Aluisio C. ^[3] ; Nixon, Douglas F. ^[1] ; Kallas, Esper G. ^{[4, 3]}

Afiliação do(s) autor(es)

^[1] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA 94143 - USA

^[2] Univ Hawaii, John A Burns Sch Med, Dept Trop Med, Hawaii Ctr AIDS, Honolulu, HI 96822 - USA

^[3] Univ Sao Paulo, Sch Med, Deparment Infect Dis, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Dept Translat Med, Sao Paulo - Brazil

^[6] Funcacao Prosangue, Hemoctr Sao Paulo, Mol Biol Lab, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 7, n. 2 FEB 2013.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 04/15856-9 - Análise prospectiva das características virológicas e imunológicas em indivíduos com infecção recente pelo HIV-1 das cidades de São Paulo e Santos, SP
• Beneficiário: Ricardo Sobhie Diaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/05845-0 - Resposta imune celular em doenças infecciosas e imunodeficiências primárias
• Beneficiário: Esper Georges Kallás
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
• Processo FAPESP: 11/12297-2 - Análise dos transcritos de miRNAs, REX e tax em células T no curso da infecção pelo HTLV-1, utilizando sequenciamento de nova geração
• Beneficiário: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Modalidade de apoio: Auxílio à Pesquisa - Regular