title: IL-12 plays a pivotal role in LFA-1-mediated T cell adhesiveness by up-regulation of CCR5 expression.
abstract: The chemokine receptor CCR5 has been implicated in the recruitment of T cells to inflammatory sites. However, the regulation of CCR5 induction on T cells and its contribution to T cell adhesiveness are poorly understood. Using a Th1 clone, 2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated 2D6(IL-12) or 2D6(IL-2), respectively), we investigated how CCR5 is induced on T cells and whether CCR5 is responsible for up-regulating the function of adhesion molecules. 2D6(IL-12) grew, forming cell aggregates, in culture containing IL-12. This was due to lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction, because 2D6(IL-12) expressed both LFA-1 and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody. Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6(IL-2) cells did not aggregate in culture with IL-2. It is important that there was a critical difference in CCR5 expression between 2D6(IL-12) and 2D6(IL-2); the former expressed high levels of CCR5, and the latter expressed only marginal levels. Both types of cells expressed detectable albeit low levels of RANTES (regulated on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18 induced high levels of RANTES mRNA expression without modulating CCR5 expression. Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6 cell aggregation. Notably, LFA-1-mediated aggregation of 2D6(IL-12) cells was suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a critical role in CCR5 expression on Th1 cells and consequently contributes to CCR5-mediated activation of LFA-1 molecules.
authors.affiliation: Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mukai
authors.forename: M
authors.initials: M
authors.lastname: Iwasaki
authors.forename: P
authors.initials: P
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Tomura
authors.forename: Y
authors.initials: Y
authors.lastname: Yashiro-Ohtani
authors.forename: S
authors.initials: S
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Murai
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: M
authors.initials: M
authors.lastname: Kogo
authors.forename: T
authors.initials: T
authors.lastname: Matsuya
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Hamaoka
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion; D002449:Cell Aggregation; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D002999:Clone Cells; D015536:Down-Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D020382:Interleukin-18; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12