scholarly journals Vaccine-Elicited 10-Kilodalton Culture Filtrate Protein-Specific CD8+ T Cells Are Sufficient To Mediate Protection against Mycobacterium tuberculosis Infection

2008 ◽  
Vol 76 (5) ◽  
pp. 2249-2255 ◽  
Author(s):  
Ying Wu ◽  
Joshua S. Woodworth ◽  
Daniel S. Shin ◽  
Sheldon Morris ◽  
Samuel M. Behar
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Culture Filtrate ◽  
Protective Immunity ◽  
Protective Antigen ◽  
T Cell Response ◽  
Rapid Expansion ◽  
Mycobacterium Tuberculosis Infection ◽  
Infected People ◽  
Culture Filtrate Protein

ABSTRACT The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are frequently recognized by T cells from infected people. The genes encoding these proteins have been deleted from the genome of the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG), and it is hypothesized that these proteins are important targets of protective immunity. Indeed, vaccination with ESAT-6 elicits protective CD4+ T cells in C57BL/6 mice. We have previously shown that M. tuberculosis infection of C3H mice elicits CFP-10-specific CD8+ and CD4+ T cells. Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a specific T-cell response only to the H-2Kk-restricted epitope CFP-1032-39. These CFP-1032-39-specific CD8+ cells undergo a rapid expansion and accumulate in the lung following challenge of immunized mice with aerosolized M. tuberculosis. Protective immunity is induced by CFP-10 DNA vaccination as measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge with M. tuberculosis. These data demonstrate that CFP-10 is a protective antigen and that CFP-1032-39-specific CD8+ T cells elicited by vaccination are sufficient to mediate protection against tuberculosis.

scholarly journals Mycobacterium bovis BCG-Specific Th17 Cells Confer Partial Protection against Mycobacterium tuberculosis Infection in the Absence of Gamma Interferon

2010 ◽  
Vol 78 (10) ◽  
pp. 4187-4194 ◽  
Author(s):  
Teresa M. Wozniak ◽  
Bernadette M. Saunders ◽  
Anthony A. Ryan ◽  
Warwick J. Britton
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Th17 Cells ◽  
Protective Immunity ◽  
Bacterial Load ◽  
Gamma Interferon ◽  
Interleukin 17 ◽  
Mycobacterium Tuberculosis Infection ◽  
Significant Prolongation ◽  
Ifn Γ

ABSTRACT Protective immunity against tuberculosis (TB) requires the integrated response of a network of lymphocytes. Both gamma interferon (IFN-γ)- and interleukin 17 (IL-17)-secreting CD4+ T cells have been identified in subjects with latent TB infection and during experimental Mycobacterium tuberculosis infection, but the contribution of Th17 cells to protective immunity is unclear. To examine their protective effects in vivo, we transferred mycobacterium-specific IL-17- and IFN-γ-secreting CD4+ T cells isolated from M. tuberculosis BCG-immunized IL-12p40−/− and IFN-γ−/− or wild-type mice, respectively, into M. tuberculosis-infected IL-12p40−/− or RAG−/− mice. In the absence of IL-12 and IL-23, neither IL-17-secreting (Th17) nor IFN-γ-secreting (Th1) BCG-specific T cells expanded or provided protection against M. tuberculosis. In RAG−/− recipients with an intact IL-12/IL-23 axis, both Th17 and Th1 cells were activated and induced significant protection against M. tuberculosis. The reduction in the bacterial load following transfer of IFN-γ−/− Th17 cells was associated with significant prolongation of survival compared to recipients of naïve IFN-γ−/− T cells. This effect was at the cost of an increased inflammatory infiltrate characterized by an excess of neutrophils. Therefore, Th17 cells can provide IFN-γ-independent protection against M. tuberculosis, and this effect may contribute to the early control of M. tuberculosis infection.

scholarly journals Involvement of IL‐17A‐producing TCR γδ T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection

2016 ◽  
Vol 4 (4) ◽  
pp. 401-412 ◽  
Author(s):  
Masayuki Umemura ◽  
Yuko Okamoto‐Yoshida ◽  
Ayano Yahagi ◽  
Seigo Touyama ◽  
Susumu Nakae ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Protective Immunity ◽  
Γδ T Cells ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection

scholarly journals High Frequency of CD4+ T Cells Specific for the TB10.4 Protein Correlates with Protection against Mycobacterium tuberculosis Infection

2006 ◽  
Vol 74 (6) ◽  
pp. 3396-3407 ◽  
Author(s):  
Sandra Hervas-Stubbs ◽  
Laleh Majlessi ◽  
Marcela Simsova ◽  
Jana Morova ◽  
Marie-Jesus Rojas ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cytotoxic T Lymphocyte ◽  
Cell Epitope ◽  
Mycobacterial Infection ◽  
T Cell Response ◽  
T Cell Epitopes ◽  
Mycobacterium Tuberculosis Infection ◽  
A Subunit

ABSTRACTTB10.4 is a newly identified antigen ofMycobacterium tuberculosisrecognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization withMycobacterium bovisBCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 peptide was identified as an immunodominant CD4+T-cell epitope forH-2dmice. Since recent results, as well as the present study, have raised interest in TB10.4 as a subunit vaccine, we analyzed immune responses induced by this antigen delivered by a new vector, the adenylate cyclase (CyaA) ofBordetella pertussis. CyaA is able to target dendritic cells and to deliver CD4+or CD8+T-cell epitopes to the major histocompatibility complex class II/I molecule presentation pathways, triggering specific Th1 or cytotoxic T-lymphocyte (CTL) responses. Several CyaA harboring either the entire TB10.4 protein or various subfragments containing the TB10.4:20-28 CTL epitope were shown to induce TB10.4-specific Th1 CD4+and CD8+T-cell responses. However, none of the recombinant CyaA, injected in the absence of adjuvant, was able to induce protection againstM. tuberculosisinfection. In contrast, TB10.4 protein administered with a cocktail of strong adjuvants that triggered a strong Th1 CD4+T-cell response induced significant protection againstM. tuberculosischallenge. These results confirm the potential value of the TB10.4 protein as a candidate vaccine and show that the presence of high frequencies of CD4+T cells specific to this strong immunogen correlates with protection againstM. tuberculosisinfection.

scholarly journals NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection

2018 ◽  
Vol 14 (8) ◽  
pp. e1007266 ◽  
Author(s):  
Shengfeng Hu ◽  
Xialin Du ◽  
Yulan Huang ◽  
Yuling Fu ◽  
Yalong Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Protective Immunity ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection

scholarly journals Mycolic acid-specific T cells protect against Mycobacterium tuberculosis infection in a humanized transgenic mouse model

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jie Zhao ◽  
Sarah Siddiqui ◽  
Shaobin Shang ◽  
Yao Bian ◽  
Sreya Bagchi ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Protective Immunity ◽  
Mycolic Acid ◽  
Human Group ◽  
Specific Group ◽  
Mycobacterium Tuberculosis Infection ◽  
Lipid Antigens ◽  
Aerosol Infection ◽  
Group 1

Group 1 CD1 molecules, CD1a, CD1b and CD1c, present lipid antigens from Mycobacterium tuberculosis (Mtb) to T cells. Mtb lipid-specific group 1 CD1-restricted T cells have been detected in Mtb-infected individuals. However, their role in protective immunity against Mtb remains unclear due to the absence of group 1 CD1 expression in mice. To overcome the challenge, we generated mice that expressed human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, mycolic-acid specific TCR (DN1Tg). Using DN1Tg/hCD1Tg mice, we found that activation of DN1 T cells was initiated in the mediastinal lymph nodes and showed faster kinetics compared to Mtb Ag85B-specific CD4+ T cells after aerosol infection with Mtb. Additionally, activated DN1 T cells exhibited polyfunctional characteristics, accumulated in lung granulomas, and protected against Mtb infection. Therefore, our findings highlight the vaccination potential of targeting group 1 CD1-restricted lipid-specific T cells against Mtb infection.

scholarly journals Mycobacterium tuberculosis Culture Filtrate Protein 10-Specific Effector/Memory CD4+and CD8+T Cells in Tubercular Pleural Fluid, with Biased Usage of T Cell Receptor Vβ Chains

2011 ◽  
Vol 79 (8) ◽  
pp. 3358-3365 ◽  
Author(s):  
Dan Qiao ◽  
Li Li ◽  
Jian Guo ◽  
Suihua Lao ◽  
Xianlan Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Pleural Fluid ◽  
Culture Filtrate ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Content Type ◽  
Culture Filtrate Protein

ABSTRACTT cell-mediated immunity is critical for the control ofMycobacterium tuberculosisinfection. Identifying the precise immune mechanisms that lead to control of initialM. tuberculosisinfection and preventing reactivation of latent infection are crucial for combating tuberculosis. However, a detailed understanding of the role of T cells in the immune response to infection has been hindered. In addition, there are few flow cytometry studies characterizing the Vβ repertoires of T cell receptors (TCRs) at local sites ofM. tuberculosisinfection in adult tuberculosis. In this study, we used culture filtrate protein 10 (CFP-10) fromM. tuberculosisto characterize T cells at local sites of infection. We simultaneously analyzed the correlation of the production of cytokines with TCR Vβ repertoires in CFP-10-specific CD4+and CD8+T cell subsets. For the first time, we demonstrate that CFP-10-specific CD4+or CD8+T cells from tubercular pleural fluid can produce high levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and upregulate the expression of CD107a/b on the cell surface. The CFP-10-specific cells were effector/memory cells with a CD45RO+CD62L−CCR7−CD27−expression profile. In addition, we found CFP-10-specific CD4+and CD8+T cells in tubercular pleural fluid, with biased usage of TCR Vβ9, Vβ12, or Vβ7.2. Our findings of CFP-10-specific CD4+and CD8+T cells in tubercular pleural fluid are critical for understanding the mechanisms of the local cellular immune response and developing more effective therapeutic interventions in cases ofM. tuberculosisinfection.

scholarly journals Cutting Edge: Control of Mycobacterium tuberculosis Infection by a Subset of Lung Parenchyma–Homing CD4 T Cells

2014 ◽  
Vol 192 (7) ◽  
pp. 2965-2969 ◽  
Author(s):  
Shunsuke Sakai ◽  
Keith D. Kauffman ◽  
Jason M. Schenkel ◽  
Cortez C. McBerry ◽  
Katrin D. Mayer-Barber ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Lung Parenchyma ◽  
Cutting Edge ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection

scholarly journals Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection

2010 ◽  
Vol 40 (8) ◽  
pp. 2211-2220 ◽  
Author(s):  
Nadia Caccamo ◽  
Giuliana Guggino ◽  
Simone A. Joosten ◽  
Giuseppe Gelsomino ◽  
Paola Di Carlo ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection

scholarly journals Comparative Analysis of B- and T-Cell Epitopes of Mycobacterium leprae and Mycobacterium tuberculosis Culture Filtrate Protein 10

2004 ◽  
Vol 72 (6) ◽  
pp. 3161-3170 ◽  
Author(s):  
John S. Spencer ◽  
Hee Jin Kim ◽  
Angela M. Marques ◽  
Mercedes Gonzalez-Juarerro ◽  
Monica C. B. S. Lima ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Culture Filtrate ◽  
Mycobacterium Leprae ◽  
Cross Reactivity ◽  
Interferon Response ◽  
Positive Staining ◽  
T Cell Epitopes ◽  
Peptide Epitopes ◽  
Culture Filtrate Protein

ABSTRACT Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a cross-reactive response against the N-terminal heterologous CFP-10 peptide, the region that exhibits the highest level of identity in the two proteins; however, the majority of peptide epitopes recognized by mouse T-cell hybridomas specific for each protein did not cross-react with heterologous peptides. Coupled with the human serology data, these results raise the possibility that peptides that could be used to differentiate infections caused by these two related microorganisms could be developed. Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis, is a secreted protein.

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