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TLR ligands efficiently convert tolerogenic CD4‐8‐ DC into immunogenic ones stimulating long‐lasting antitumor immune response
Author(s) -
Zhang Xueshu,
Xiang Jim
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.18
Subject(s) - cd80 , cd40 , cd86 , adjuvant , immune system , cd8 , dendritic cell , ctl* , immunology , chemistry , cancer research , biology , cytotoxic t cell , t cell , in vitro , biochemistry
Different dendritic cell (DC) subsets play distinct roles in immune responses. CD4 − 8 − DC secreting transforming growth factor (TGF)‐β stimulate CD4 + regulatory T type 1 (Tr1) cell responses leading to antitumor immune tolerance. CD4 − 8 − DC could be converted into inducing Th1 rather Tr1 by being cultured for another 16–24 hrs and pulsed with 1 mg/ml OVA protein. In this study we investigate whether TLR ligands, agonist anti‐CD40 and their combinations could more efficiently convert CD4 − 8 − DC to induce Th1 response. We found that CpG, LPS and anti‐CD40 alone or CpG+anti‐CD40, but not LPS+anti‐CD40 stimulate those DCs to express similar higher level of CD40, CD54, CD80, CD86 and I‐Ab after 8hrs culture than newly isolated DCs; Among the above groups, CpG group showed the strongest capacity of stimulating the proliferation of OT1 CD8 and OTII CD4 T cells and induced 100% animal protection from tumor challenge with highest OVAI specific CTL ratio and in vivo cytotoxicity; LPS+anti‐CD40 group was the weakest in every above aspect and could not provide any animal protection. Taken together, our findings indicate that CpG 8 hrs treatment could convert tolerogenic DC into immunogenic ones provoking strong antitumor immunity; and TLR ligands plus anti‐CD40 combination should be carefully tested before using as adjuvant for DC maturation. Thus our results might have great impact on designing the future tumor vaccine.