The frequency of CD127low expressing CD4+CD25high 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.
BACKGROUND
CD4+CD25high regulatory T (TReg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg 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 TReg 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 IFNgamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load.


CONCLUSIONS
Taken together, the results suggest that TReg 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 CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.
Michaëlsson
Jakob
J
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Jakob.michaelsson@ki.se
Barbosa
Hugo Marcelo R
HM
Jordan
Kimberley A
KA
Chapman
Joan M
JM
Brunialti
Milena K C
MK
Neto
Walter Kleine
WK
Nukui
Youko
Y
Sabino
Ester C
EC
Chieia
Marco Antonio
MA
Oliveira
Acary Souza Bulle
AS
Nixon
Douglas F
DF
Kallas
Esper G
EG
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015490:HTLV-I Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019562:Viral Load
D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007371:Interferon-gamma