Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells

PLoS Pathog. 2012;8(7):e1002771. doi: 10.1371/journal.ppat.1002771. Epub 2012 Jul 19.


Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+) T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blastomyces / immunology
  • Blastomyces / pathogenicity
  • Blastomycosis / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Fungal Vaccines / immunology*
  • Hepatocyte Nuclear Factor 1-alpha
  • Histoplasma / immunology
  • Histoplasma / pathogenicity
  • Histoplasmosis / immunology
  • Immunocompromised Host
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Memory / immunology
  • Interleukin-12 / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Lectins, C-Type / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lung Diseases, Fungal / immunology*
  • Lung Diseases, Fungal / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology
  • Pneumonia / immunology*
  • Pneumonia / microbiology
  • Receptors, CCR6 / biosynthesis
  • Receptors, CCR6 / metabolism
  • Receptors, CXCR3 / biosynthesis
  • Receptors, Immunologic / biosynthesis
  • Signal Transduction
  • T Cell Transcription Factor 1 / biosynthesis
  • Th17 Cells / immunology*


  • CCR6 protein, mouse
  • Cxcr3 protein, mouse
  • Fungal Vaccines
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, CCR6
  • Receptors, CXCR3
  • Receptors, Immunologic
  • T Cell Transcription Factor 1
  • dectin 1
  • Interleukin-12