title: Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses.
abstract: Prevalence of pro-inflammatory diseases is rising in developed country populations. The increase in these diseases has fuelled the search for new, immune suppressive, anti-inflammatory therapies, which do not impact, or minimally impact, CD4(+) and/or CD8(+) T-cell-mediated immunity. The goal of this study was to determine if antigen-presenting cells (APCs) activated by the anti-inflammatory oligosaccharide, lacto-N-fucopentaose III (LNFPIII), would have an impaired ability to drive CD4(+) T helper (Th) or CD8(+) memory and effector T-cell responses. To investigate this we activated splenic dendritic cells (SDCs) with LNFPIII and examined their ability to drive antigen-specific CD4(+) Th, and CD8(+) memory and cytotoxic T-cell (CTL) responses compared with lipopolysaccharide (LPS) -stimulated SDCs. The LNFPIII-activated SDCs had altered co-stimulatory molecule expression compared with LPS-stimulated SDCs, while the levels of SDC chemokines following activation by either compound were similar. LNFPIII-activated SDCs produced significantly lower levels of interleukin-12 but surprisingly higher levels of interleukin-6 than LPS-activated SDCs. Similar to previous studies using bone-marrow-derived DCs, LNFPIII-activated SDCs induced strong Th2 responses in vivo and ex vivo. LNFPIII activation of APCs was independent of the Toll-interleukin-1 receptor adaptor myeloid differentiating factor 88. Importantly, LNFPIII-matured DCs induced CD8(+) memory and effector CTL responses similar to those driven by LPS-matured DCs, including the frequency of interferon-gamma-producing CD8(+) T cells and induction of CTL effectors. Treatment of APCs by the anti-inflammatory glycan LNFPIII did not impair their ability to drive CD8(+) effector and memory cell-mediated immunity.
authors.affiliation: School of Biochemistry & Molecular Biology, Australian National University, Linnaeus Way, Canberra, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Akram A
authors.initials: AA
authors.lastname: Da'Dara
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.forename: Donald A
authors.initials: DA
authors.lastname: Harn
mesh_terms: D000606:Amino Sugars / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D011134:Polysaccharides / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000606:Amino Sugars; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011134:Polysaccharides; C434666:lacto-N-fucopentaose III; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin