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CXCR5+ T helper cells mediate protective immunity against tuberculosis
Samantha R. Slight, … , Troy D. Randall, Shabaana A. Khader
Samantha R. Slight, … , Troy D. Randall, Shabaana A. Khader
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(2):712-726. https://doi.org/10.1172/JCI65728.
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Research Article Immunology

CXCR5+ T helper cells mediate protective immunity against tuberculosis

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Abstract

One third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we demonstrated that organized ectopic lymphoid structures containing CXCR5+ T cells were present in Mtb-infected lungs. In addition, we found that in experimental Mtb infection models, the presence of CXCR5+ T cells within ectopic lymphoid structures was associated with immune control. Furthermore, in a mouse model of Mtb infection, we showed that activated CD4+CXCR5+ T cells accumulated in Mtb-infected lungs and produced proinflammatory cytokines. Mice deficient in Cxcr5 had increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We demonstrated that CXCR5 expression in T cells mediated correct T cell localization within TB granulomas, promoted efficient macrophage activation, protected against Mtb infection, and facilitated lymphoid follicle formation. These data demonstrate that CD4+CXCR5+ T cells play a protective role in the immune response against TB and highlight their potential use for future TB vaccine design and therapy.

Authors

Samantha R. Slight, Javier Rangel-Moreno, Radha Gopal, Yinyao Lin, Beth A. Fallert Junecko, Smriti Mehra, Moises Selman, Enrique Becerril-Villanueva, Javier Baquera-Heredia, Lenin Pavon, Deepak Kaushal, Todd A. Reinhart, Troy D. Randall, Shabaana A. Khader

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Figure 4

Activated CD4+CXCR5+ T cells accumulate in the lung during Mtb infection and express both Tfh-like and Th1-like cell markers.

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Activated CD4+CXCR5+ T cells accumulate in the lung during Mtb infection...
B6 mice were infected as in Figure 3. (A) The frequency and number of activated CD4+CXCR5+ T cells were determined by flow cytometry at different time points after infection. (B) Frequency and number of activated (CD44hi) and unactivated (CD44lo) CD4+CXCR5+ T cells were determined in Mtb-infected lungs on day 25 after infection by flow cytometry. A typical histogram showing CXCR5-specific staining (filled) within activated CD4+ T cells and relevant isotype control antibody (open) is shown (B). Expression of ICOS and PD-1 (C), IFN-γ, TNF-α, and IL-2 (D), and Tbet and Bcl6 (E) on activated (CD44hi) and unactivated (CD44lo) CD4+CXCR5+ and CD4+CXCR5– T cells was calculated by determining the mean fluorescence intensity using flow cytometry. A typical histogram showing expression of PD-1 and ICOS (filled) and relevant isotype control antibody (open) on activated CD4+CXCR5+ cells is shown (C). The data points represent the mean (±SD) of values from 4–6 mice (A–E). *P = 0.05, **P = 0.005, ***P = 0.0005. One experiment representative of 2.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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