CXCR5+ T helper cells mediate protective immunity against tuberculosis

Shabaana Khader of the University of Pittsburgh discusses the identification of immune parameters that distinguish active and latent TB infections. Highlights:

  • One third of the world's population is infected with Mycobacterium tuberculosis; however, only 5-10% will develop active infections.
  • Individuals with latent infections have a 10% lifetime risk of developing active tuberculosis. This risk increases to 10% per year in the presence of HIV infection. It is therefore important to identify immunologic features that distinguish active TB from latent.
  • Granulomas are immune cell aggregates that are a hallmark of TB infection. They play a protective role in latent TB, but can promote infection during active TB.
  • Using human, non-human primate, and mouse models of TB infection, Khader and colleagues identified a subset of T helper cells (CXCR5+) that are associated with protective granulomas in latent TB.
  • These results identify a previously unexpected role for CXCR5 in the control of TB infection and could be used to improve TB vaccine strategies.

Published January 2, 2013, by The JCI

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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 February 1, 2013; First 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

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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