Characterization of regulatory T cells identified as CD4+CD25highCD39+ in patients with active tuberculosis

被引:63
作者
Chiacchio, T. [1 ]
Casetti, R. [2 ]
Butera, O. [1 ]
Vanini, V. [1 ]
Carrara, S. [1 ]
Girardi, E. [1 ]
Di Mitri, D. [3 ]
Battistini, L. [3 ]
Martini, F. [2 ]
Borsellino, G. [3 ]
Goletti, D. [1 ]
机构
[1] Ist Nazl Malattie Infett L Spallanzani, IRCCS, Translat Res Unit, I-00149 Rome, Italy
[2] Ist Nazl Malattie Infett L Spallanzani, IRCCS, Cellular Immunol Lab, Dept Epidemiol & Preclin Res, I-00149 Rome, Italy
[3] Santa Lucia Fdn, Lab Neuroimmunol, Rome, Italy
关键词
CD39; FoxP3; RD1; proteins; TB; T-reg; EXPRESSION; DISEASE; STIMULATION; SUPPRESSION; ANTIGENS; IMMUNITY; BLOOD;
D O I
10.1111/j.1365-2249.2009.03908.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Forkhead box P3 (FoxP3) is a transcription factor whose expression characterizes regulatory T cells (T-reg), but it is also present on activated T cells, thus hindering correct T-reg identification. Using classical markers for T-reg recognition, discordant results were found in terms of T-reg expansion during active tuberculosis (TB) disease. Recently CD39 has been shown to be an accurate marker for T-reg detection. The objectives of this study were: (i) to identify T-reg expressing CD39 in patients with TB and to compare the results with those obtained by the standard phenotypic markers; (ii) to evaluate if T-reg are expanded in vitro by exogenous interleukin (IL)-2 or by antigen-specific stimulation; and (iii) to characterize T-reg function on the modulation of antigen-specific responses. We enrolled 13 patients with pulmonary TB and 12 healthy controls. T-reg were evaluated by flow cytometry ex vivo and after antigen-specific in vitro stimulation using CD25, FoxP3, CD127 and CD39 markers. Results indicate that CD39(+) cells within the CD4(+)CD25(high) cells have T-reg properties (absence of interferon-gamma production and transforming growth factor-beta 1 release upon stimulation). Ex vivo analysis did not show significant differences between TB patients and controls of T-reg by classical or novel markers. In contrast, a significantly higher percentage of T-reg was found in TB patients after antigen-specific stimulation both in the presence or absence of IL-2. Depletion of CD39(+) T-reg increased RD1-specific responses significantly. In conclusion, CD39 is an appropriate marker for T-reg identification in TB. These results can be useful for future studies to monitor Mycobacterium tuberculosis-specific response during TB.
引用
收藏
页码:463 / 470
页数:8
相关论文
共 19 条
[1]   Natural regulatory T cells in infectious disease [J].
Belkaid, Y ;
Rouse, BT .
NATURE IMMUNOLOGY, 2005, 6 (04) :353-360
[2]   Expression of ectonucleotidase CD39 by Foxp3+ Treg cells:: hydrolysis of extracellular ATP and immune suppression [J].
Borsellino, Giovanna ;
Kleinewietfeld, Markus ;
Di Mitri, Diletta ;
Sternjak, Alexander ;
Diamantini, Adamo ;
Giometto, Raffaella ;
Hoepner, Sabine ;
Centonze, Diego ;
Bernardi, Giorgio ;
Dell'Acqua, Maria Luisa ;
Rossini, Paolo Maria ;
Battistini, Luca ;
Rotzschke, Olaf ;
Falk, Kirsten .
BLOOD, 2007, 110 (04) :1225-1232
[3]   CD4+CD25+FoxP3+ regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease [J].
Chen, Xinchun ;
Zhou, Boping ;
Li, Meizhong ;
Deng, Qunyi ;
Wu, Xueqiong ;
Le, Xiaohua ;
Wu, Chi ;
Larmonier, Nicolas ;
Zhang, Wei ;
Zhang, Hongmei ;
Wang, Huosheng ;
Katsanis, Emmanuel .
CLINICAL IMMUNOLOGY, 2007, 123 (01) :50-59
[4]   Diagnostic standards and classification of tuberculosis in adults and children [J].
Dunlap, NE ;
Bass, J ;
Fujiwara, P ;
Hopewell, P ;
Horsburgh, CR ;
Salfinger, M ;
Simone, PM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (04) :1376-1395
[5]   Global epidemiology of tuberculosis [J].
Dye, C .
LANCET, 2006, 367 (9514) :938-940
[6]   Region of difference 1 antigen-specific CD4+ memory T cells correlate with a favorable outcome of tuberculosis [J].
Goletti, Delia ;
Butera, Ornella ;
Bizzoni, Federica ;
Casetti, Rita ;
Girardi, Enrico ;
Poccia, Fabrizio .
JOURNAL OF INFECTIOUS DISEASES, 2006, 194 (07) :984-992
[7]   Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis [J].
Guyot-Revol, V ;
Innes, JA ;
Hackforth, S ;
Hinks, T ;
Lalvani, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 173 (07) :803-810
[8]   In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans [J].
Hougardy, Jean-Michel ;
Verscheure, Virginie ;
Locht, Camille ;
Mascart, Franqoise ;
Mascart, Francoise .
MICROBES AND INFECTION, 2007, 9 (11) :1325-1332
[9]   Regulatory T cells depress immune responses to protective antigens in active tuberculosis [J].
Hougardy, Jean-Michel ;
Place, Sammy ;
Hildebrand, Marc ;
Drowart, Annie ;
Debrie, Anne-Sophie ;
Locht, Camille ;
Mascart, Francoise .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 176 (04) :409-416
[10]   Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4 [J].
Joosten, Simone A. ;
van Meijgaarden, Krista E. ;
Savage, Nigel D. L. ;
de Boert, Tjitske ;
Triebel, Frederic ;
van der Wal, Annemieke ;
de Heer, Emile ;
Klein, Michel R. ;
Geluk, Annemieke ;
Ottenhoff, Tom H. M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (19) :8029-8034