title: Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.
abstract: Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonic epithelial cells and in various colonic epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Okazawa
authors.forename: T
authors.initials: T
authors.lastname: Kanai
authors.forename: K
authors.initials: K
authors.lastname: Nakamaru
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Ogata
authors.forename: Y
authors.initials: Y
authors.lastname: Iwao
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Kawamura
authors.forename: S
authors.initials: S
authors.lastname: Makita
authors.forename: K
authors.initials: K
authors.lastname: Uraushihara
authors.forename: R
authors.initials: R
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D002455:Cell Division; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019409:Interleukin-15 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology*; D053728:Interleukin-18 Receptor beta Subunit; D007376:Interleukin-2 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C115629:IL18RAP protein, human; D019409:Interleukin-15; D020382:Interleukin-18; D053728:Interleukin-18 Receptor beta Subunit; D007376:Interleukin-2; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020170:Caspase 1