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Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T‐lymphocyte responses and antitumour immunity
Author(s) -
Hao Siguo,
Bai Ou,
Li Fang,
Yuan Jinying,
Laferte Suzanne,
Xiang Jim
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02483.x
Subject(s) - cd80 , biology , dendritic cell , cytotoxic t cell , cd86 , immune system , cd8 , microbiology and biotechnology , major histocompatibility complex , immunology , acquired immune system , mhc class ii , antigen presenting cell , cd40 , t cell , in vitro , biochemistry
Summary Exosomes (EXO) derived from dendritic cells (DC), which express major histocompatibility complex (MHC) and costimulatory molecules, have been used for antitumour vaccines. However, they are still less effective by showing only prophylatic immunity in animal models or very limited immune responses in clinical trials. In this study, we showed that ovalbumin (OVA) protein‐pulsed DC (DC OVA )‐derived EXO (EXO OVA ) displayed MHC class I–OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll‐like receptor 4 (TLR4), TLR9, MyD88 and DC‐SIGN molecules, but at a lower level than DC OVA . EXO OVA can be taken up by DC through LFA‐1/CD54 and C‐type lectin/mannose (glucosamine)‐rich C‐type lectin receptor (CLR) interactions. Mature DC pulsed with EXO OVA , which were referred to as mDC EXO , expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC OVA . The mDC EXO could more strongly stimulate OVA‐specific CD8 + T‐cell proliferation in vitro and in vivo , and more efficiently induce OVA‐specific cytotoxic T‐lymphocyte responses, antitumour immunity and CD8 + T‐cell memory in vivo than EXO OVA and DC OVA . In addition, mDC EXO could also more efficiently eradicate established tumours. Therefore, mature DC pulsed with EXO may represent a new, highly effective DC‐based vaccine for the induction of antitumour immunity.