Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells
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Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells Kazunori Onoe´ Æ Yoshiki Yanagawa Æ Keita Minami Æ Norifumi Iijima Æ Kazuya Iwabuchi
Published online: 1 June 2007 Humana Press Inc. 2007
Abstract If Th1 or Th2 polarization could be artificially manipulated, effective immune responses would be generated depending on nature of the targets. In this study we attempted to regulate CD40 expressions on dendritic cells (DCs) in order to modify the T cell response. It was found that reducing agents selectively inhibited surface expression of CD40 on DCs. This finding may provide a new strategy of DC-mediated modulation of the Th1/Th2 balance. It was also shown that NKT-produced Th1/Th2 cytokine balance was under control of negative feedback loop through DCs. Th1 cytokine-pretreated DCs mainly induced Th2 cytokine production, whereas Th2 cytokine-pretreated DCs induced Th1 cytokine production by a-galactosylceramide-stimulated NKT cells. The negative feedback regulation system could be applicable to therapeutics of various diseases based on immunological disorders. Keywords Th1/Th2 Dendritic cells NKT cells Feedback regulation CD40 Anti-cancer IFN-c
Introduction Immunological responses can be divided into two types, T helper 1 (Th1) and T helper 2 (Th2). In the Th1 system, interferon (IFN)-c, interleukin (IL)-2, and tumor necrosis factor (TNF)-a play a major role in protective immunity against viruses, bacteria, and tumors (Table 1). However, the Th1 immunity sometimes aggravates certain types of autoimmune diseases and athrosclerosis [1–3]. On the other hand, IL-4, IL-10, and IL-13 play a role in Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006. K. Onoe´ (&) Y. Yanagawa K. Minami N. Iijima K. Iwabuchi Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Kita-15, Nishi-7, Sapporo 060-0815, Japan e-mail: [email protected]
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Immunol Res (2007) 38:319–332
Table 1 Two aspects of Th1 and Th2 responses Th1 response (Cellular)
(1) Mediated by IFN-c, IL-2, TNF-a (2) Generates protective responses against viruses, bacteria, and tumor cells (3) Aggravates certain types of autoimmune diseases and atherosclerosis
Th2 response (Humoral)
(1) Mediated by IL-4, IL-10, IL-13 (2) Generates protective responses against parasites (3) Regulates unfavorable responses (i.e., autoimmune diseases) (4) Aggravates allergy
Th2 type immunity. The Th2 system is important in anti-parasite reaction, and regulates auto-immune diseases, but aggravates allergy [4, 5]. Naive T cells differentiate into Th1 or Th2 cells, which are influenced by the environmental condition around these helper T cells. For instance, IL-12 produced by dendritic cells (DCs) promotes Th1 differentiation [6], whereas IL-4 produced by Th2 cells favors induction of Th2 cells in an autocrine manner, and establishes Th2 polarization [4, 7]. We also reported that TNF-a enhanced preference of DCs for Th2 differentiation [8]. The Th1 or Th2 type determ
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