Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity

• DOI: 10.1038/ni943
• Publication Date: 2003-05-30T15:07:38Z
• Authors: Kenji Kabashima; Takahiko Murata; Hiroyuki Tanaka; Toshiyuki Matsuoka; Daiji Sakata; Nobuaki Yoshida; Koko Katagiri; Tatsuo Kinashi; Toshiyuki Tanaka; Masayuki Miyasaka; Hiroichi Nagai; Fumitaka Ushikubi; Shuh Narumiya
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; T-Lymphocytes; Receptors, Thromboxane; Immunity; Cell Communication; Dendritic Cells; Dermatitis, Contact; Lymphocyte Activation; 3. Good health; Mice, Inbred C57BL; Mice; Thromboxane A2; 03 medical and health sciences; Hyaluronan Receptors; 0302 clinical medicine; Cell Movement; Animals; Female; Lymphatic Diseases

Physical interaction of T cells and dendritic cells (DCs) is essential for T cell proliferation and differentiation, but it has been unclear how this interaction is regulated physiologically. Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP). In vitro, a TP agonist enhances random cell movement (chemokinesis) of naive but not memory T cells, impairs DC-T cell adhesion, and inhibits DC-dependent proliferation of T cells. In vivo, immune responses to foreign antigens are enhanced in TP-deficient mice, which also develop marked lymphadenopathy with age. Similar immune responses were seen in wild-type mice treated with a TP antagonist during the sensitization period. Thus, TXA2-TP signaling modulates acquired immunity by negatively regulating DC-T cell interactions.