title: Sulfatide administration leads to inhibition of HIV-1 replication and enhanced hematopoeisis.
abstract: The pathogenesis of HIV-1 infection is a complex process in which Natural Killer (NK) and Natural Killer T (NKT) cells play an important role. NKT cells express markers for NK cells and a TCR of the conventional T cells and recognize lipid antigens presented by the non-polymorphic CD1 molecule. CD1d-restricted type I NKT cells express an invariant TCR and can recognize αGalCer, whereas a major subset of type II NKT expressing diverse TCR can recognize a self-glycolipid, sulfatide. It has been shown that CD4+ type I NKT cells are infected by HIV-1 and decreased in HIV-1-infected individuals. However, their exact role in HIV-1 infection as well as the biology and function of the type II NKT cell subset in HIV-1 infection and disease progression are not known. Our earlier studies have shown that activation of CD1d-restricted type II NKT cells by sulfatide and their interactions with plasmacytoid dendritic (pDC) and myeloid dendritic (mDC) cells result in anergy induction in type I NKT cells in several models. Here we used SCID-Hu (Thy/Liv) animals, co-implanted with human fetal liver and thymus, and found that these implants contain both type I and type II NKT cells, CD161+CD3+ NKT cells, NK cells and dendritic cells during HIV-infection. We found that the administration of sulfatide (bi-weekly, 20 μg/animal, i.p.) in SCID-Hu animals inhibits HIV-1 replication more efficiently than treatment with the nucleoside analog reverse transcriptase inhibitor, AZT. Virus replication was lowered significantly up to 4-8 weeks post infection. Furthermore sulfatide administration also resulted in significant retention of hematopoeisis that is lost during HIV-1 infection. Advantageously, sulfatide administration itself was not associated with anemia or bone marrow suppression, that are severe side effects of HAART. Since the CD1d-mediated immune pathway is highly conserved between rodents and humans, sulfatide treatment may represent a novel HLA-independent approach for intervention of HIV-1 pathogenesis.
authors.affiliation: Laboratories of Stem Cell Biology, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
authors.forename: I Birgitta
authors.initials: IB
authors.lastname: Sundell
authors.forename: Ramesh
authors.initials: R
authors.lastname: Halder
authors.forename: Menghua
authors.initials: M
authors.lastname: Zhang
authors.forename: Igor
authors.initials: I
authors.lastname: Maricic
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Koka
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000821:virology; D013433:Sulfoglycosphingolipids / Q000008:administration & dosage* / Q000494:pharmacology; D018800:Thy-1 Antigens / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D013433:Sulfoglycosphingolipids; D018800:Thy-1 Antigens