IL-18 stimulates IL-13-mediated IFN-gamma-sensitive host resistance in vivo.
IL-4 and IL-13 are up-regulated during in vivo responses to many nematode parasites, but increasing evidence suggests that increases in IL-13 can also occur independently of the IL-4-dominant Th2 response. Blocking B7 after Trichuris muris inoculation inhibits resistance and IL-4 elevations, instead resulting in an IFN-gamma-dominant response associated with susceptibility. However, blocking IFN-gamma under these conditions restores IL-13-dependent resistance. In this study, we examined the mechanism of IL-13 up-regulation and associated protection during this in vivo immune response. CD4+ T cells and DX5+ TCR- cells were identified as the major producers of IL-13, and the DX5+ TCR- cells were phenotyped as NK cells, since they expressed CD11b, IL-2Rbeta and Ly49C but not c-kit or Fc epsilonRI. NK cell-derived IL-13 elevations were T cell-dependent, as CD4+ T cell depletion blocked IL-13 production by mesenteric lymph node cells and induced susceptibility. IL-13 expression was increased independently of IL-12; however, blocking IL-18 function inhibited IL-13 production and increased susceptibility. These results indicate that CD4+ T cells and NK cells are the major sources of IL-13 during the in vivo Th1 response induced by B7 blockade and that under these conditions, IL-18 is specifically required for the in vivo up-regulation of IL-13 production and associated host protection.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Qian
Q
Liu
Zhugong
Z
Liu
Jeannette
J
Whitmire
Farhang
F
Alem
Hossein
H
Hamed
John
J
Pesce
Joseph F
JF
Urban
William C
WC
Gause
D000069594:Abatacept; D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018796:Immunoconjugates / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000502:physiology; D014257:Trichuriasis / Q000276:immunology*
D018122:B7-1 Antigen; D018796:Immunoconjugates; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D020382:Interleukin-18; D021122:Protein Subunits; D018664:Interleukin-12; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma