CD4+ CD25highforkhead box protein 3+ regulatory T lymphocytes suppress interferon-γ and CD107 expression in CD4+and CD8+ T cells from tuberculous pleural effusions

被引:25
作者
Geffner, L. [1 ]
Basile, J. I. [1 ]
Yokobori, N. [1 ]
Sabio y Garcia, C. [1 ]
Musella, R. [2 ]
Castagnino, J. [2 ]
Sasiain, M. C. [1 ]
de la Barrera, S. [1 ]
机构
[1] Acad Nacl Med Buenos Aires, IMEX CONICET, RA-1425 Buenos Aires, DF, Argentina
[2] Hosp Francisco Muniz, Dept Neumonol, Buenos Aires, DF, Argentina
关键词
CD107; pleural effusions; T regulatory; tuberculosis; GROWTH-FACTOR-BETA; MYCOBACTERIUM-TUBERCULOSIS; PERIPHERAL-BLOOD; CYTOTOXIC ACTIVITY; EFFECTOR; SEVERITY; SUBSETS; DISEASE; INTERLEUKIN-4; RECRUITMENT;
D O I
10.1111/cei.12227
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (T-reg) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of T-reg (CD4(+)CD25(high)forkhead box protein 3(+)), interferon (IFN)- and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+)CD25(+), CD4(+)CD25(high)FoxP3(+) and CD8(+)CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+)CD25(low/neg)IL-10(+) in PB and CD4(+)CD25(low/neg)IFN-(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+)CD107(+) and CD8(+)CD107(+) cells was observed in PF. T-reg depletion enhanced the in-vitro M. tuberculosis-induced IFN- and CD4(+) and CD8(+) degranulation responses and decreased CD4(+)IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy T-reg cells effectively inhibit not only IFN- expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.
引用
收藏
页码:235 / 245
页数:11
相关论文
共 47 条
[1]   Correlation between interleukin-10 and in situ necrosis and fibrosis suggests a role for interleukin-10 in the resolution of the granulomatous response of tuberculous pleurisy patients [J].
Barbosa, Theolis ;
Arruda, Sergio ;
Chalhoub, Marcelo ;
Oliveira, Fabiano ;
Melo, Jose F., Jr. ;
Fidelis, Ramon ;
Neto, Antonio N. ;
Barbosa, Aryon A., Jr. ;
Barral-Netto, Manoel .
MICROBES AND INFECTION, 2006, 8 (03) :889-897
[2]  
BARNES PF, 1989, J IMMUNOL, V142, P1114
[3]   Mycobacterial lipopeptides elicit CD4+ CTLs in Mycobacterium tuberculosis-infected humans [J].
Bastian, Max ;
Braun, Tobias ;
Bruns, Heiko ;
Roellinghoff, Martin ;
Stenger, Steffen .
JOURNAL OF IMMUNOLOGY, 2008, 180 (05) :3436-3446
[4]   TUBERCULOUS PLEURISY [J].
BERGER, HW ;
MEJIA, E .
CHEST, 1973, 63 (01) :88-92
[5]   Sensitive and viable identification of antigen-specific CD8+T cells by a flow cytometric assay for degranulation [J].
Betts, MR ;
Brenchley, JM ;
Price, DA ;
De Rosa, SC ;
Douek, DC ;
Roederer, M ;
Koup, RA .
JOURNAL OF IMMUNOLOGICAL METHODS, 2003, 281 (1-2) :65-78
[6]   CD4+ and CD8+ T cells kill intracellular Mycobacterium tuberculosis by a perforin and Fas/Fas ligand-independent mechanism [J].
Canaday, DH ;
Wilkinson, RJ ;
Li, Q ;
Harding, CV ;
Silver, RF ;
Boom, WH .
JOURNAL OF IMMUNOLOGY, 2001, 167 (05) :2734-2742
[7]   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
[8]   Specific lytic activity against mycobacterial antigens is inversely correlated with the severity of tuberculosis [J].
De la Barrera, SS ;
Finiasz, M ;
Frias, A ;
Alemán, M ;
Barrionuevo, P ;
Fink, S ;
Franco, MC ;
Abbate, E ;
Sasiain, MD .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 132 (03) :450-461
[9]   In vitro synthesis of interferon-γ, interleukin-4, transforming growth factor-β and interleukin-1β by peripheral blood mononuclear cells from tuberculosis patients:: Relationship with the severity of pulmonary involvement [J].
Dlugovitzky, D ;
Bay, ML ;
Rateni, L ;
Urizar, L ;
Rondelli, CFM ;
Largacha, C ;
Farroni, MA ;
Molteni, O ;
Bottasso, OA .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1999, 49 (02) :210-217
[10]   Polyfunctional Mycobacterium tuberculosis-specific effector memory CD4+ T cells at sites of pleural TB [J].
El Fenniri, L. ;
Toossi, Z. ;
Aung, H. ;
El Iraki, G. ;
Bourkkadi, J. ;
Benamor, J. ;
Laskri, A. ;
Berrada, N. ;
Benjouad, A. ;
Mayanja-Kizza, H. ;
Betts, M. R. ;
El Aouad, R. ;
Canaday, D. H. .
TUBERCULOSIS, 2011, 91 (03) :224-230