Human NKT cells express granulysin and exhibit antimycobacterial activity

Jennifer L. Gansert, Viviane Kießler, Matthias Engele, Frederick Wittke, Martin Röllinghoff, Alan M. Krensky, Steven A. Porcelli, Robert L. Modlin, Steffen Stenger

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Human NKT cells are a unique subset of T cells that express an invariant Vα24 TCR that recognizes the nonclassical Agpresenting molecule CD1d. Activation of NKT cells is greatly augmented by the marine sponge-derived glycolipid α-galactosylceramide (αGalCer). Because human monocyte-derived cells express CD1d and can harbor the intracellular pathogen Mycobacterium tuberculosis, we asked whether the addition of αGalCer could be used to induce effector functions of NKT cells against infected monocytes, macrophages, and monocyte-derived dendritic cells. NKT cells secreted IFN-γ, proliferated, and exerted lytic activity in response to αGalCer-pulsed monocyte-derived cells. Importantly, αGalCer-activated NKT cells restricted the growth of intracellular M. tuberculosis in a CD1d-dependent manner. NKT cells that exhibited antimycobacterial activity also expressed granulysin, an antimicrobial peptide shown to mediate an antimycobacterial activity through perturbation of the mycobacterial surface. Degranulation of NKT cells resulted in depletion of granulysin and abrogation of antimycobacterial activity. The detection of CD1d in granulomas of tuberculosis patients supports the potential interaction of NKT cells with CD1d-expressing cells at the site of disease activity. These studies provide evidence that αGalCer-activated CD1d-restricted T cells can participate in human host defense against M. tuberculosis infection.

Original languageEnglish (US)
Pages (from-to)3154-3161
Number of pages8
JournalJournal of Immunology
Volume170
Issue number6
StatePublished - Mar 15 2003

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Natural Killer T-Cells
Galactosylceramides
Mycobacterium tuberculosis
Monocytes
CD1d Antigen
Mycobacterium Infections
Glycolipids
Porifera
T-Lymphocyte Subsets
Granuloma
Dendritic Cells
Tuberculosis
Macrophages
T-Lymphocytes
Peptides
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Gansert, J. L., Kießler, V., Engele, M., Wittke, F., Röllinghoff, M., Krensky, A. M., ... Stenger, S. (2003). Human NKT cells express granulysin and exhibit antimycobacterial activity. Journal of Immunology, 170(6), 3154-3161.

Human NKT cells express granulysin and exhibit antimycobacterial activity. / Gansert, Jennifer L.; Kießler, Viviane; Engele, Matthias; Wittke, Frederick; Röllinghoff, Martin; Krensky, Alan M.; Porcelli, Steven A.; Modlin, Robert L.; Stenger, Steffen.

In: Journal of Immunology, Vol. 170, No. 6, 15.03.2003, p. 3154-3161.

Research output: Contribution to journalArticle

Gansert, JL, Kießler, V, Engele, M, Wittke, F, Röllinghoff, M, Krensky, AM, Porcelli, SA, Modlin, RL & Stenger, S 2003, 'Human NKT cells express granulysin and exhibit antimycobacterial activity', Journal of Immunology, vol. 170, no. 6, pp. 3154-3161.
Gansert JL, Kießler V, Engele M, Wittke F, Röllinghoff M, Krensky AM et al. Human NKT cells express granulysin and exhibit antimycobacterial activity. Journal of Immunology. 2003 Mar 15;170(6):3154-3161.
Gansert, Jennifer L. ; Kießler, Viviane ; Engele, Matthias ; Wittke, Frederick ; Röllinghoff, Martin ; Krensky, Alan M. ; Porcelli, Steven A. ; Modlin, Robert L. ; Stenger, Steffen. / Human NKT cells express granulysin and exhibit antimycobacterial activity. In: Journal of Immunology. 2003 ; Vol. 170, No. 6. pp. 3154-3161.
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