Invariant V alpha 14+ NKT cells participate in the early response to enteric Listeria monocytogenes infection.
Invariant Valpha14(+) NKT cells are a specialized CD1-reactive T cell subset implicated in innate and adaptive immunity. We assessed whether Valpha14(+) NKT cells participated in the immune response against enteric Listeria monocytogenes infection in vivo. Using CD1d tetramers loaded with the synthetic lipid alpha-galactosylceramide (CD1d/alphaGC), we found that splenic and hepatic Valpha14(+) NKT cells in C57BL/6 mice were early producers of IFN-gamma (but not IL-4) after L. monocytogenes infection. Adoptive transfer of Valpha14(+) NKT cells derived from TCRalpha degrees Valpha14-Jalpha18 transgenic (TCRalpha degrees Valpha14Tg) mice into alymphoid Rag(null) gamma(c)(null) mice demonstrated that Valpha14(+) NKT cells were capable of providing early protection against enteric L. monocytogenes infection with systemic production of IFN-gamma and reduction of the bacterial burden in the liver and spleen. Rechallenge experiments demonstrated that previously immunized wild-type and Jalpha18null mice, but not TCRalpha(null) or TCRalpha(null) Valpha14Tg mice, were able to mount adaptive responses to L. monocytogenes. These data demonstrate that Valpha14(+) NKT cells are able to participate in the early response against enteric L. monocytogenes through amplification of IFN-gamma production, but are not essential for, nor capable of, mediating memory responses required to sterilize the host.
Unité des Cytokines et Développement Lymphoïde, Institut National de la Santé et de la Recherche Médicale Unité 668, Institut Pasteur, 25 Rue du Docteur Roux, Cedex 15 Paris, France.
Thomas
T
Ranson
Søren
S
Bregenholt
Agnes
A
Lehuen
Olivier
O
Gaillot
Maria C
MC
Leite-de-Moraes
André
A
Herbelin
Patrick
P
Berche
James P
JP
Di Santo
D000818:Animals; D002469:Cell Separation; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D007441:Intubation, Gastrointestinal; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors; D015533:Transcriptional Activation / Q000276:immunology
D007371:Interferon-gamma