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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

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Michaelsson, Jakob [1, 2] ; Barbosa, Hugo Marcelo R. [3] ; Jordan, Kimberley A. [1] ; Chapman, Joan M. [1] ; Brunialti, Milena K. C. [3] ; Neto, Walter Kleine [4] ; Nukui, Youko [4] ; Sabino, Ester C. [4] ; Chieia, Marco Antonio [3] ; Bulle Oiliveira, Acary Souza [3] ; Nixon, Douglas F. [1] ; Kallas, Esper G. [3, 5]
Total Authors: 12
Affiliation:
[1] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA - USA
[2] Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm - Sweden
[3] Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo - Brazil
[4] Sao Paulo Blood Bank, Sao Paulo - Brazil
[5] Univ Sao Paulo, Clin Immunol & Allergy Div, BR-05508 Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: BMC IMMUNOLOGY; v. 9, JUL 29 2008.
Web of Science Citations: 17
Abstract

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases. (AU)