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Guangzhou, China

Fu X.,Sun Yat Sen University | Liu Y.,Sun Yat Sen University | Li L.,Sun Yat Sen University | Li Q.,Sun Yat Sen University | And 5 more authors.
Immunology | Year: 2011

Natural killer (NK) cells are known as innate immune lymphocytes that respond rapidly when challenged by pathogens but little is known about adaptive immune features including memory related to NK cells from human beings. In the present study, we demonstrate for the first time that human NK cells expressing the memory-associated marker CD45RO were persistent in pleural fluid cells (PFCs) from tuberculous patients. CD45RO+ NK cells produced significantly more interferon-γ and were more cytotoxic compared with CD45RO- NK cells from PFCs when stimulated with interleukin-12 (IL-12). Consistently, IL-12 enhanced the expression of granzyme B, CD69, CD25, NKG2D, IL-12 receptors β1 and β2 on CD45RO+ NK cells from PFCs. Our experiments contribute to a better understanding of the NK cells from PFCs and indicate that human CD45RO+ NK cells from PFCs expressing a 'memory-like' phenotype may have an important role in defending against infection by Mycobacterium tuberculosis. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd. Source


Wu C.,Sun Yat Sen University | Li Z.,Sun Yat Sen University | Fu X.,Sun Yat Sen University | Yu S.,Sun Yat Sen University | And 2 more authors.
Oncotarget | Year: 2015

Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis. However, the function of CD3+TCRvβ11+ NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL- 17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45ROhighCD62LlowCCR7low. Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3+TCRvβ11+ NKT cells. Sorted CD3+TCRvβ11+ NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3+TCRvβ11+ NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3+TCRvβ11+ NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection. Source


Fu X.,Sun Yat Sen University | Yang B.,Sun Yat Sen University | Lao S.,Chest Hospital of Guangzhou | Fan Y.,Sun Yat Sen University | Wu C.,Sun Yat Sen University
Clinical Immunology | Year: 2013

We have previously shown that human memory-like NK cells were persistent in tuberculous pleurisy but it was unclear how NK cells migrated into the pleural fluids. At present, we found that NK cells from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs. Migration assay demonstrated that IP-10 and SDF-1 induced more migration of NK cells from PFCs than PBMCs. CD45RO+ or CD45RO- NK cells from PFCs were co-cultured with autologous monocytes and stimulated with BCG. The results showed CD45RO+ but not CD45RO- NK cells produced significantly higher levels of IFN-γ, which was IL-12-dependent since anti-IL-12Rβ1 mAbs could significantly inhibit the IFN-γ by NK cells. Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection. © 2013 Elsevier Inc. Source


Li L.,Sun Yat Sen University | Qiao D.,Sun Yat Sen University | Zhang X.,Chest Hospital of Guangzhou | Liu Z.,Chest Hospital of Guangzhou | Wu C.,Sun Yat Sen University
Immunobiology | Year: 2011

Most of the studies evaluating the function of tuberculosis (TB)-specific T cells were only based on the ability to produce cytokines, which may not fully reflect the function of T cells. In the present study, we confirmed that Bacille Calmette Guerin (BCG) could significantly induce cytokine production by CD4+ T cells from BCG-vaccinated PPD+ donors. In addition, CD4+ T cells were activated, divided and proliferated in response to BCG stimulation. Phenotypic analysis showed that IFN-γ+CD4+ T cells displayed CD45RA-CCR7+/-CD62L-, indicating that these CD4+ T cells were central and effector memory cells. The analysis of cytokine profiles demonstrated that most of BCG-specific BrdU+CD4+ T cells produced Th1 cytokines in response to polyclonal stimulation. In addition, we found that regulatory T cells (Treg) suppressed BCG-induced proliferation and IFN-γ production by memory CD4+ T cells. The suppressive effects of Treg on BCG-specific responses of CD4+ T cells could be partially reversed by blocking the production of IL-10. Taken together, our results demonstrated that functional central and effector memory BCG-specific CD4+ T cells could be detected based on the activation, proliferation and division of these cells, and modulated by Treg in PBMCs from BCG-vaccinated PPD+ donors. © 2010 Elsevier GmbH. Source


Li L.,Sun Yat Sen University | Yang B.,Sun Yat Sen University | Zhang X.,Chest Hospital of Guangzhou | Lao S.,Chest Hospital of Guangzhou | Wu C.,Sun Yat Sen University
Tuberculosis | Year: 2014

Increasing evidences in animals and humans suggest that CD8+ T cells contribute significantly to immune defenses against Mycobacterium tuberculosis (Mtb). In the present study, we found that without any stimulation, CD8+ T cells in pleural fluid cells (PFCs) expressed significantly higher levels of CD69 than PBMCs from patients with tuberculous pleurisy (TBP). CD8+CD69+ T cells expressed significantly higher levels of CD45RO and HLA-DR and lower levels of CD45RA than CD8+CD69 - T cells, demonstrating that CD8+CD69+ T cells were activated memory cells. Furthermore, we found higher expression of CCR6 and lower expression of CCR7 and CD62L on CD8+CD69+ T cells compared with CD8+CD69- T cells, suggesting that the expression of CCR6 and reduced expression of CCR7 and CD62L might facilitate the migration of circulating CD8+CD69+ T cells into tuberculous pleural space. Importantly, following stimulation with culture filtrate protein of 10 kDa (CFP10) peptides, CD8+CD69+ T cells but not CD8+CD69- T cells expressed CD107a/b, IFN-γ and TNF-α, demonstrating that CD8+CD69+ T cells were MTB-specific cells. In addition, the majority of CD8 +CD69+ T cells were dominated by polyfunctional T cells. In summary, we demonstrated that CD69 as a useful marker for MTB-specific CD8+ T cells in PFCs from patients with TBP enabled a direct ex vivo estimation of the quantity, as well as the quality, of MTB-specific CD8 + responses. © 2014 Elsevier Ltd. All rights reserved. Source

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