title: A microbial glycolipid functions as a new class of target antigen for delayed-type hypersensitivity.
abstract: Delayed-type hypersensitivity (DTH) is marked by high levels of protein antigen-specific T cell responses in sensitized individuals. Recent evidence has revealed a distinct pathway for T cell immunity directed against glycolipid antigens, but DTH to this class of antigen has been undetermined and difficult to prove due to their insolubility in aqueous solutions. Here, glucose monomycolate (GMM), a highly hydrophobic glycolipid of the cell wall of mycobacteria, was dispersed in aqueous solutions in the form of octaarginine-modified liposomes and tested for its ability to elicit cutaneous DTH responses in bacillus Calmette-Guerin (BCG)-immunized guinea pigs. After an intradermal challenge with the GMM liposome, a significant skin induration was observed in BCG-immunized, but not mock-treated, animals. The skin reaction peaked at around 2 days with local infiltration by mononuclear cells, and therefore, the response shared basic features with the classical DTH to protein antigens. Lymph node T cells from BCG-immunized guinea pigs specifically increased IFN-γ transcription in response to the GMM liposome, and this response was completely blocked by antibodies to CD1 lipid antigen-presenting molecules. Finally, whereas the T cells increased transcription of both T helper (Th) 1-type (IFN-γ and TNF-α) and Th2-type (IL-5 and IL-10) cytokines in response to the purified protein derivative or tuberculin, their GMM-specific response was skewed to Th1-type cytokine production known to be critical for protection against tuberculosis. Thus, our study reveals a novel form of DTH with medical implications.
authors: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors: Takaya
authors: T
authors: Komori
authors: Takashi
authors: T
authors: Nakamura
authors: Isamu
authors: I
authors: Matsunaga
authors: Daisuke
authors: D
authors: Morita
authors: Yuki
authors: Y
authors: Hattori
authors: Hirotaka
authors: H
authors: Kuwata
authors: Nagatoshi
authors: N
authors: Fujiwara
authors: Kenji
authors: K
authors: Hiromatsu
authors: Hideyoshi
authors: H
authors: Harashima
authors: Masahiko
authors: M
authors: Sugita
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006017:Glycolipids / Q000737:chemistry*; D006168:Guinea Pigs; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008198:Lymph Nodes / Q000473:pathology; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D006017:Glycolipids; D015848:Interleukin-5; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma