Lacto-N-fucopentaose III found on Schitosoma mansoni egg antigens functions as adjuvant for proteins by inducing Th2-type response

被引:180
作者
Okano, M
Satoskar, AR
Nishizaki, K
Harn, DA
机构
[1] Okayama Univ, Sch Med, Dept Otolaryngol, Okayama 7008558, Japan
[2] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
关键词
D O I
10.4049/jimmunol.167.1.442
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have recently demonstrated that induction of Th2 responses by Schistosoma mansoni egg Ag is largely due to carbohydrates on the Ag functioning as adjuvants. Lacto-N-fucopentaose III (LNFPIII), a polylactosamine sugar, is the predominant carbohydrate found in S. mansoni egg Ag. Therefore, using neoglycoprotein, we investigated whether LNFPIII induces in vivo Th2 response and functions as an adjuvant. Following intranasal immunization with LNFPIII linked to human serum albumin (HSA) (HSA-LNFPIII), BALB/c mice mounted a strong Th2 response and produced significantly higher levels of total IgE as well as HSA-specific IgG, IgG1, and IgE. HSA-LNFPIII was over 1000-fold more potent in inducing Ab production as compared with HSA alone. Although LNFPIII itself did not function as an epitope for either IgG or IgE, its conjugation with protein was essential for the adjuvant activity. Moreover, fucose residue on LNFPIII was crucial for induction of Ab production. Nasal lymphocytes from mice immunized with HSA-LNFPIII produced IL-4, IL-5, and IL-10, but not IFN-gamma following in vitro stimulation with HSA or HSA-LNFPIII. In addition, these activated nasal lymphocytes also showed a significant increase of B7-2 expression on B220-positive cells. Furthermore, not only intranasal but also both l.p. and s.c. immunization with HSA-LNFPIII induced significant production of HSA-specific Abs compared with the immunization with HSA alone, suggesting that the activity of LNFPIII was not restricted on particular route of immunization. These results demonstrate that Lewis type carbohydrate LNFPIII can function as an adjuvant by their ability to induce a Th2 response. The Journal of Immunology, 2001.
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页码:442 / 450
页数:9
相关论文
共 28 条
[1]   CHARACTERIZATION OF MOUSE NASAL LYMPHOCYTES ISOLATED BY ENZYMATIC EXTRACTION WITH COLLAGENASE [J].
ASANUMA, H ;
INABA, Y ;
AIZAWA, C ;
KURATA, T ;
TAMURA, SI .
JOURNAL OF IMMUNOLOGICAL METHODS, 1995, 187 (01) :41-51
[2]   B70 ANTIGEN IS A 2ND LIGAND FOR CTLA-4 AND CD28 [J].
AZUMA, M ;
ITO, D ;
YAGITA, H ;
OKUMURA, K ;
PHILLIPS, JH ;
LANIER, LL ;
SOMOZA, C .
NATURE, 1993, 366 (6450) :76-79
[3]   In interleukin-4-deficient mice, alum not only generates T helper 1 responses equivalent to Freund's complete adjuvant, but continues to induce T helper 2 cytokine production [J].
Brewer, JM ;
Conacher, M ;
Satoskar, A ;
Bluethmann, H ;
Alexander, J .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (09) :2062-2066
[4]   Milk oligosaccharide profiles by reversed-phase HPLC of their perbenzoylated derivatives [J].
Chaturvedi, P ;
Warren, CD ;
RuizPalacios, GM ;
Pickering, LK ;
Newburg, DS .
ANALYTICAL BIOCHEMISTRY, 1997, 251 (01) :89-97
[5]   CARBOHYDRATE-DEPENDENT, HLA CLASS II-RESTRICTED, HUMAN T-CELL RESPONSE TO THE BEE VENOM ALLERGEN PHOSPHOLIPASE-A2 IN ALLERGIC PATIENTS [J].
DUDLER, T ;
ALTMANN, F ;
CARBALLIDO, JM ;
BLASER, K .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (02) :538-542
[6]   UPTAKE OF PNEUMOCYSTIS-CARINII MEDIATED BY THE MACROPHAGE MANNOSE RECEPTOR [J].
EZEKOWITZ, RAB ;
WILLIAMS, DJ ;
KOZIEL, H ;
ARMSTRONG, MYK ;
WARNER, A ;
RICHARDS, FF ;
ROSE, RM .
NATURE, 1991, 351 (6322) :155-158
[7]   A MULTIVALENT LACTO-N-FUCOPENTAOSE-III LYSYLLYSINE CONJUGATE DECOMPACTS PREIMPLANTATION MOUSE EMBRYOS, WHILE THE FREE OLIGOSACCHARIDE IS INEFFECTIVE [J].
FENDERSON, BA ;
ZEHAVI, U ;
HAKOMORI, SI .
JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (05) :1591-1596
[8]   INTERFERENCE WITH HIV-INDUCED SYNCYTIUM FORMATION AND VIRAL INFECTIVITY BY INHIBITORS OF TRIMMING GLUCOSIDASE [J].
GRUTERS, RA ;
NEEFJES, JJ ;
TERSMETTE, M ;
DEGOEDE, REY ;
TULP, A ;
HUISMAN, HG ;
MIEDEMA, F ;
PLOEGH, HL .
NATURE, 1987, 330 (6143) :74-77
[9]  
GRZYCH JM, 1991, J IMMUNOL, V146, P1322
[10]  
HOFF SD, 1989, CANCER RES, V49, P6883