TY - JOUR
T1 - Human NKT cells express granulysin and exhibit antimycobacterial activity
AU - Gansert, Jennifer L.
AU - Kießler, Viviane
AU - Engele, Matthias
AU - Wittke, Frederick
AU - Röllinghoff, Martin
AU - Krensky, Alan M.
AU - Porcelli, Steven A.
AU - Modlin, Robert L.
AU - Stenger, Steffen
PY - 2003/3/15
Y1 - 2003/3/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.170.6.3154
DO - 10.4049/jimmunol.170.6.3154
M3 - Article
C2 - 12626573
AN - SCOPUS:0037443555
SN - 0022-1767
VL - 170
SP - 3154
EP - 3161
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -