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.
引用
收藏
页码:442 / 450
页数:9
相关论文
共 28 条
[21]   THE MANNOSE RECEPTOR AND OTHER MACROPHAGE LECTINS [J].
STAHL, PD .
CURRENT OPINION IN IMMUNOLOGY, 1992, 4 (01) :49-52
[22]   Biology, biochemistry and immunology of carcinoma-associated mucins [J].
TaylorPapadimitriou, J ;
Finn, OJ .
IMMUNOLOGY TODAY, 1997, 18 (03) :105-107
[23]  
USUI M, 1979, J IMMUNOL, V122, P1266
[24]  
Van Neerven RJJ, 1998, CLIN EXP ALLERGY, V28, P808
[25]   SELECTIN LIGANDS [J].
VARKI, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7390-7397
[26]  
Velupillai P, 1997, J IMMUNOL, V158, P338
[27]   OLIGOSACCHARIDE-SPECIFIC INDUCTION OF INTERLEUKIN-10 PRODUCTION BY B220+ CELLS FROM SCHISTOSOME-INFECTED MICE - A MECHANISM FOR REGULATION OF CD4+ T-CELL SUBSETS [J].
VELUPILLAI, P ;
HARN, DA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (01) :18-22
[28]   COSTIMULATION OF T-CELL GROWTH [J].
YANG, L ;
LINSLEY, PS .
CURRENT OPINION IN IMMUNOLOGY, 1992, 4 (03) :265-270