Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens.
Infection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-gamma than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-gamma in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.
Hayashi
N
N
Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Matsui
K
K
Tsutsui
H
H
Osada
Y
Y
Mohamed
R T
RT
Nakano
H
H
Kashiwamura
S
S
Hyodo
Y
Y
Takeda
K
K
Akira
S
S
Hada
T
T
Higashino
K
K
Kojima
S
S
Nakanishi
K
K
D000818:Animals; D017951:Antigen Presentation; D000947:Antigens, Helminth / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008018:Life Cycle Stages / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010063:Ovum / Q000254:growth & development / Q000276:immunology; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D013997:Time Factors
D000947:Antigens, Helminth; D016207:Cytokines; D015847:Interleukin-4