Research article

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

Jakob Michaëlsson^1,5* , Hugo Marcelo R Barbosa^2* , Kimberley A Jordan¹ , Joan M Chapman¹ , Milena KC Brunialti² , Walter Kleine Neto³ , Youko Nukui³ , Ester C Sabino³ , Marco Antonio Chieia² , Acary Souza Bulle Oliveira² , Douglas F Nixon¹ and Esper G Kallas^2,4

¹  Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA

²  Infectious Diseases Division, Federal University of São Paulo, São Paulo, Brazil

³  São Paulo Blood Bank, São Paulo, Brazil

⁴  Clinical Immunology and Allergy Division, University of São Paulo, Brazil

⁵  Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

author email corresponding author email* Contributed equally

BMC Immunology 2008, 9:41doi:10.1186/1471-2172-9-41

Published:	29 July 2008

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-I drives activation, spontaneous IFNγ 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^highCD127^low phenotype. T_Reg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.