Premium
Dendritic cell tumor‐antigen processing and activation of tumor‐specific T cells
Author(s) -
Gerner Michael Y,
Casey Kerry A,
Mescher Matthew F
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.22.2_supplement.527
Subject(s) - cd80 , cd86 , cd40 , cross presentation , dendritic cell , antigen presentation , cd8 , mhc class ii , antigen , t cell , antigen presenting cell , mhc class i , biology , microbiology and biotechnology , mhc restriction , chemistry , major histocompatibility complex , cytotoxic t cell , immunology , immune system , in vitro , biochemistry
Steady‐state dendritic cell (DC) presentation of tumor antigens (TAg) on MHC‐I/II in draining LN (DLN) and tumor sites, as well as the respective responses of naïve T cells, are poorly characterized. Using a weakly immunogenic murine melanoma, we found that immature CD8a+ DC efficiently cross‐presented TAg on MHC‐I and caused CD8 T cell tolerance in the DLN. Conversely, CD4 T cells were ignorant throughout tumor growth due to specific inhibition of DC MHC‐II presentation at the DLN and tumor sites. Tumors contained a surprisingly high number of infiltrating DC (TIDC) that phenotypically resembled dermal DC by expressing CD11b+CD8a‐B220‐CD4‐EpCAM‐GR1−/+ surface markers, but displayed an altered activation phenotype, with relatively low levels of I‐Ab and CD40 but high levels of CD80 and CD86. The TIDC were efficient at in vivo phagocytosis and pinocytosis, but failed to express substantial MHC‐II peptide complexes on the cell surface and were poor at migration to DLN. These results suggest that inhibition of TAg processing for MHC‐II presentation in TIDC results in CD4 T cell ignorance and prevents CD8a+ DC licensing in DLN. AI34824 (M.F.M.); CA82596 (M.F.M.); NCI 2 T32 CA009138‐31 (M.Y.G.)