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Distinct In Vivo and In Vitro Cytokine Profiles of Draining Lymph Node Cells in Acute and Chronic Phases of Contact Hypersensitivity: Importance of a Type 2 Cytokine-Rich Cutaneous Milieu for the Development of an Early-Type Response in the Chronic Phase¹

Hideki Kitagaki^*,, Momoko Kimishima^*, Yuichi Teraki^*, Jun Hayakawa^*, Kazuhito Hayakawa^*, Shigeki Fujisawa and Tetsuo Shiohara^2,*

^* Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan; and Ako Research Institute, Otsuka Pharmaceutical Co., Hyogo, Japan

Although regional lymph nodes (LN) have been extensively studied as rich sources of effector T cells in contact hypersensitivity (CH), it remains unknown whether T cell responses in the LN reflect those in effector skin sites. We previously showed that repeated elicitation of CH results in a shift in the time course of Ag-specific CH from a delayed-type hypersensitivity response to an early-type response, a reflection of a shift in cutaneous cytokine expression from a type 1 to a type 2 profile. To investigate whether repeated elicitation of CH could also drive T cell development to the type 2 phenotype in the regional draining LN, sequential cytokine gene expression after hapten application was assessed during both the acute and the chronic phase of CH. In the draining LN the shift to type 2 cytokine production was also observed, but more mixed patterns of responses were induced than in the corresponding skin sites. The chronic LN cells (LNC), when stimulated in vitro, produced markedly lower levels of type 1 cytokines and higher levels of type 2 cytokines than the acute LNC. A successful passive transfer of an early-type response by the LNC was only induced in the recipient mice when the skin sites chronically treated with hapten were elicited. These results indicate that an early-type response by regional LNC would take place only in a milieu with sufficient levels of type 2 cytokines.

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