scholarly journals Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6

2020 ◽  
Author(s):  
Uma Shanmugasundaram ◽  
Allison N Bucsan ◽  
Shashank R. Ganatra ◽  
Chris Ibegbu ◽  
Melanie Quezada ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Double Positive ◽  
Cell Responses ◽  
Ifn Γ

AbstractMycobacterium tuberculosis (Mtb)-specific T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a non-human primate (NHP) aerosol model, we studied the kinetics, phenotypes and functions of Mtb antigen-specific T cells in peripheral and lung compartments of Mtb-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage (BAL), for up to 24 weeks post-infection. We found significantly higher frequencies of Mtb-specific effector and memory CD4 and CD8 T cells producing IFN-γ in the airways compared to peripheral blood, which were maintained throughout the study period. Moreover, Mtb-specific IL-17+ and IL-17/IFN-γ double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17 responses are associated with LTBI. The majority of Mtb-specific CD4 T cells that homed to the airways expressed the chemokine receptor CXCR3 and co-expressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and non-granulomatous regions of the lung and inversely correlated with Mtb burden. Our findings provide novel insights into antigen-specific T cell responses associated with asymptomatic Mtb infection that are relevant for developing better strategies to control TB.

scholarly journals Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259829
Author(s):  
Heni Muflihah ◽  
Manuela Flórido ◽  
Leon C. W. Lin ◽  
Yingju Xia ◽  
James A. Triccas ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Influenza A ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Influenza A Viruses ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses ◽  
Subcutaneous Immunization

The current Mycobacterium bovis BCG vaccine provides inconsistent protection against pulmonary infection with Mycobacterium tuberculosis. Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after M. tuberculosis infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of M. tuberculosis infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant M. tuberculosis CD4+ T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic M. tuberculosis infection. Boosting BCG with rIAVs increased the frequency of IFN-γ-secreting specific T cells (p<0.001) and polyfunctional CD4+ T cells (p<0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection against M. tuberculosis compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased M. tuberculosis-specific memory T cell responses in the lung, but not protection against M. tuberculosis infection.

scholarly journals CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Vaccine ◽  
2010 ◽  
Vol 28 (51) ◽  
pp. 8183-8188 ◽  
Author(s):  
Patrícia C.C. Neves ◽  
Richard A. Rudersdorf ◽  
Ricardo Galler ◽  
Myrna C. Bonaldo ◽  
Marlon Gilsepp Veloso de Santana ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Gamma Delta ◽  
Cell Responses ◽  
Ifn Γ ◽  
Yellow Fever Vaccination

Mycobacterium tuberculosis Rv3615c is a highly immunodominant antigen and specifically induces potent Th1-type immune responses in tuberculosis pleurisy

2017 ◽  
Vol 131 (15) ◽  
pp. 1859-1876 ◽  
Author(s):  
Jiangping Li ◽  
Juan Shen ◽  
Suihua Lao ◽  
Xiaomin Li ◽  
Jie Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd4 T Cells ◽  
Specific Antigen ◽  
T Cell Responses ◽  
Tuberculosis Infection ◽  
Effector Memory ◽  
Cell Responses ◽  
Immunodominant Antigen

T-cell responses have been demonstrated to be essential for preventing Mycobacterium tuberculosis infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2, and TNF-α, not only limit the invasion of M. tuberculosis but also eliminate the pathogen at the site of infection. Bacillus Calmette–Guérin (BCG) is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components, in addition to those expressed in BCG, and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity. Here, we studied human pulmonary T-cell responses induced by the M. tuberculosis-specific antigen Rv3615c, a protein with a similar size and sequence homology to ESAT-6 and CFP-10, which induced dominant CD4+ T-cell responses in human tuberculosis (TB) models. We characterized T-cell responses including cytokine profiling, kinetics of activation, expansion, differentiation, TCR usage, and signaling of activation induced by Rv3615c compared with other M. tuberculosis-specific antigens. The expanded CD4+ T cells induced by Rv3615c predominately produced Th1, but less Th2 and Th17, cytokines and displayed effector/memory phenotypes (CD45RO+CD27−CD127−CCR7−). The magnitude of expansion and cytokine production was comparable to those induced by well-characterized the 6 kDa early secreted antigenic target (ESAT-6), the 10 kDa culture filtrate protein (CFP-10) and BCG. Rv3615c contained multiple epitopes Rv3615c1–15, Rv3615c6–20, Rv3615c66–80, Rv3615c71–85 and Rv3615c76–90 that activated CD4+ T cells. The Rv3615c-specific CD4+ T cells shared biased of T-cell receptor variable region of β chain (TCR Vβ) 1, 2, 4, 5.1, 7.1, 7.2 and/or 22 chains to promote their differentiation and proliferation respectively, by triggering a signaling cascade. Our data suggest that Rv3615c is a major target of Th1-type responses and can be a highly immunodominant antigen specific for M. tuberculosis infection.

Impact of inducible co-stimulatory molecule (ICOS) on T-cell responses and protection against Mycobacterium tuberculosis infection

2011 ◽  
Vol 41 (4) ◽  
pp. 981-991 ◽  
Author(s):  
Geraldine Nouailles ◽  
Tracey A. Day ◽  
Stefanie Kuhlmann ◽  
Delia Loewe ◽  
Anca Dorhoi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses

scholarly journals Induction of Mycobacterium tuberculosis-Specific Primary and Secondary T-Cell Responses in Interleukin-15-Deficient Mice

2005 ◽  
Vol 73 (5) ◽  
pp. 2910-2922 ◽  
Author(s):  
Vanja Lazarevic ◽  
David J. Yankura ◽  
Sherrie J. Divito ◽  
JoAnne L. Flynn
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Effector T Cells ◽  
Cell Responses ◽  
Interleukin 15 ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Several studies have provided evidence that interleukin-15 (IL-15) can enhance protective immune responses against Mycobacterium tuberculosis infection. However, the effects of IL-15 deficiency on the functionality of M. tuberculosis-specific CD4 and CD8 T cells are unknown. In this study, we investigated the generation and maintenance of effector and memory T-cell responses following M. tuberculosis infection of IL-15−/− mice. IL-15−/− mice had slightly higher bacterial numbers during chronic infection, which were accompanied by an increase in gamma interferon (IFN-γ)-producing CD4 and CD8 T cells. There was no evidence of increased apoptosis or a defect in proliferation of CD8 effector T cells following M. tuberculosis infection. The induction of cytotoxic and IFN-γ CD8 T-cell responses was normal in the absence of IL-15 signaling. The infiltration of CD4 and CD8 T cells into the lungs of “immune” IL-15−/− mice was delayed in response to M. tuberculosis challenge. These findings demonstrate that efficient effector CD4 and CD8 T cells can be developed following M. tuberculosis infection in the absence of IL-15 but that recall T-cell responses may be impaired.

scholarly journals Maintenance of Peripheral T Cell Responses during Mycobacterium tuberculosis Infection

2012 ◽  
Vol 189 (9) ◽  
pp. 4451-4458 ◽  
Author(s):  
William W. Reiley ◽  
Susan T. Wittmer ◽  
Lynn M. Ryan ◽  
Sheri M. Eaton ◽  
Laura Haynes ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses
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