期刊
MUCOSAL IMMUNOLOGY
卷 8, 期 5, 页码 1099-1109出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2014.136
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资金
- Children's Hospital of Pittsburgh
- NIH [HL105427]
- Children's Hospital of Pittsburgh Research Advisory Committee Grant from Children's Hospital of Pittsburgh of the UPMC Health System
- American Lung Association [RT-30592]
- Department of Molecular Microbiology, Washington University St Louis
- Alexander and Gertrude Berg Fellowship
- Department of Medicine, University of Rochester
- Washington University in St Louis
- [U19 AI91036]
Tuberculosis (TB) vaccine development has focused largely on targeting T helper type 1 (Th1) cells. However, despite inducing Th1 cells, the recombinant TB vaccine MVA85A failed to enhance protection against TB disease in humans. In recent years, Th17 cells have emerged as key players in vaccine-induced protection against TB. However, the exact cytokine and immune requirements that enable Th17-induced recall protection remain unclear. In this study, we have investigated the requirements for Th17 cell-induced recall protection against Mycobacterium tuberculosis (Mtb) challenge by utilizing a tractable adoptive transfer model in mice. We demonstrate that adoptive transfer of Mtb-specific Th17 cells into naive hosts, and upon Mtb challenge, results in Th17 recall responses that confer protection at levels similar to vaccination strategies. Importantly, although interleukin (IL)-23 is critical, IL-12 and IL-21 are dispensable for protective Th17 recall responses. Unexpectedly, we demonstrate that interferon-gamma (IFN-gamma) produced by adoptively transferred Th17 cells impairs long-lasting protective recall immunity against Mtb challenge. In contrast, CXCR5 expression is crucial for localization of Th17 cells near macrophages within well-formed B-cell follicles to mediate Mtb control. Thus, our data identify new immune characteristics that can be harnessed to improve Th17 recall responses for enhancing vaccine design against TB.
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