TY - JOUR
T1 - Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner
AU - Sano, Kunio
AU - Shirota, Hidekazu
AU - Terui, Tadashi
AU - Hattori, Toshio
AU - Tamura, Gen
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - The outcomes of immune responses are regulated by various parameters including how Ags are handled by APCs. In this study, we describe the intrinsic immunomodulatory characteristics of oligodeoxynucleotides (ODNs) that improve the Ag presentation by APCs. ODNs (20-mer) containing CpG motifs induced strong Th1-skewed responses. In contrast, those without CpG motifs enhanced cytokine production by effector Th cells without particular skewing toward Th1 responses or induced the differentiation of unprimed CD4+ T cells toward Th2 cells. These functional features were prominently envisaged when ODNs were conjugated to the Ag, and were underlain by the facilitated binding of ODN-conjugated Ag to Ia+ cells. Despite the functional differences between ODNs with CpG motifs and those without CpG motifs, both ODNs bound to Ia+ cells with similar affinity and kinetics. Immunoenhancing activities of the ODNs were not sequence-dependent; the characteristics, including the facilitation of Ag capture, enhancement of effector Th cell responses, and induction of Th2 cells, were shared by randomly synthesized ODNs conjugated to Ag. This is the first study suggesting that ODNs, independent of the sequences, enhance immune responses through the promoted capture of ODN-conjugated Ag by APCs.
AB - The outcomes of immune responses are regulated by various parameters including how Ags are handled by APCs. In this study, we describe the intrinsic immunomodulatory characteristics of oligodeoxynucleotides (ODNs) that improve the Ag presentation by APCs. ODNs (20-mer) containing CpG motifs induced strong Th1-skewed responses. In contrast, those without CpG motifs enhanced cytokine production by effector Th cells without particular skewing toward Th1 responses or induced the differentiation of unprimed CD4+ T cells toward Th2 cells. These functional features were prominently envisaged when ODNs were conjugated to the Ag, and were underlain by the facilitated binding of ODN-conjugated Ag to Ia+ cells. Despite the functional differences between ODNs with CpG motifs and those without CpG motifs, both ODNs bound to Ia+ cells with similar affinity and kinetics. Immunoenhancing activities of the ODNs were not sequence-dependent; the characteristics, including the facilitation of Ag capture, enhancement of effector Th cell responses, and induction of Th2 cells, were shared by randomly synthesized ODNs conjugated to Ag. This is the first study suggesting that ODNs, independent of the sequences, enhance immune responses through the promoted capture of ODN-conjugated Ag by APCs.
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U2 - 10.4049/jimmunol.170.5.2367
DO - 10.4049/jimmunol.170.5.2367
M3 - Article
C2 - 12594259
AN - SCOPUS:0037371208
VL - 170
SP - 2367
EP - 2373
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -