| Full text | |
| Author(s): Show less - |
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]
Total Authors: 11
|
| Affiliation: | [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
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | PLoS Neglected Tropical Diseases; v. 7, n. 2 FEB 2013. |
| Web of Science Citations: | 9 |
| Abstract | |
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) | |
| FAPESP's process: | 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos |
| Grantee: | Ricardo Sobhie Diaz |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 10/05845-0 - Cellular immune responses in infectious diseases and primary immunodeficiencies |
| Grantee: | Esper Georges Kallás |
| Support Opportunities: | Research Grants - Visiting Researcher Grant - International |
| FAPESP's process: | 11/12297-2 - Profiling the human T-cells miRNA, REX and tax transcriptomes in the course of HTLV-1 infection using a deep sequencing approach |
| Grantee: | Sabri Saeed Mohammed Ahmed Al-Sanabani |
| Support Opportunities: | Regular Research Grants |