title: Dominant expression of CXCR3 is associated with induced expression of IP-10 at hapten-challenged sites of murine contact hypersensitivity: a possible role for interferon-gamma-producing CD8(+) T cells in IP-10 expression.
abstract: Murine contact hypersensitivity is elicited as a consequence of immunologic reactions triggered by skin-applied antigen, interactions among Langerhans cells, T cells, keratinocytes and mast cells, and a variety of chemokines generated by cellular interactions. In this study, we sensitized and challenged BALB/c mice with hapten, dinitrofluorobenzene or picryl chloride, and examined the expressions of mRNA for chemokines and their receptors by reverse transcription-polymerase chain reaction in the skin of elicited earlobes. CXC chemokines, IP-10 and Mig, were transcribed 24-48 h after challenge. This was associated with the expression of their agonistic receptor CXCR3, while mRNA for TARC and MDC, and their receptor CCR4 were not detected. Since CXCR3 and CCR4 are expressed preferentially on types 1 (Th1/Tc1) and 2 (Th2) T cells, respectively, the results suggested that the former type of T cells predominantly infiltrate at the elicited sites. Immune lymph node cells of the sensitized mice also expressed mRNA for CXCR3 but not CCR4 with concomitant transcription of interferon-gamma (IFN-gamma) but not interleukin-4 subsequent to challenge. The percentage of lymph node CD8(+) T cells was increased from 16% in naive mice to 30-50% in hapten-challenged mice, and in the immune lymph nodes, CD8(+) cells were the major source of IFN-gamma compared to CD4(+) cells. Since IFN-gamma is known to stimulate keratinocytes to produce IP-10 and Mig, it is suggested that these IFN-gamma-producing CD8(+) T cells enhance the production of these chemokines, thereby functioning as not only the effector cells but also the cytokine source to sustain the challenge reaction.
authors.affiliation: Department of Dermatology, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui Prefecture, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tokuriki
authors.forename: Naohiro
authors.initials: N
authors.lastname: Seo
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kumakiri
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
chemical_list: C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D006241:Haptens; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene; D010853:Picryl Chloride