Invariant Valphal4~+ NKT Cells Participate in the Early Response to Enteric Listeria monocytogenes Infection

摘要

Invariant Valphal4~+ NKT cells are a specialized CDl-reactive T cell subset implicated in innate and adaptive immunity.We assessed whether Valphal4~+ NKT cells participated in the immune response against enteric Listeria monocytogenes infection in vivo.Using CDld tetramers loaded with the synthetic lipid alpha-galactosylceramide(CDld/alphaGC),we found that splenic and hepatic Valphal4~+ NKT cells in C57BL/6 mice were early producers of IFN-gamma(but not IL-4)after L.monocytogenes infection.Adoptive transfer of Valphal4~+ NKT cells derived from TCRalpha~deg Valphal4-Jalpha18 transgenic(TCRalpha~degValphal4Tg)mice into alymphoid Rag deg gamma_c deg mice demonstrated that Valphal4~+ 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 Jalpha18deg mice,but not TCRalpha~deg or TCRalpha~degValphal4Tg mice,were able to mount adaptive responses to L.monocytogenes.These data demonstrate that Valphal4~+ 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.