Antigen processing and MHC-II presentation by dermal and tumor-infiltrating dendritic cells.
MHC-II presentation by dendritic cells (DC) is necessary both for initial priming of CD4 T cells and for induction of peripheral effector function. Although CD4 T cells can be critical for competent immunization-mediated cancer immunosurveillance, unmanipulated CD4 T cell responses to poorly immunogenic tumors result in either complete ignorance or tolerance induction, suggesting inadequate DC function. In this study, we investigated the phenotype, Ag uptake, and MHC-II presentation capacity of normal dermal DC and tumor-infiltrating DC (TIDC) in both lymphoid and peripheral sites. We found that murine tumors were extensively infiltrated by partially activated TIDC that closely resembled dermal DC by surface marker expression. However, in contrast to dermal DC, TIDC were inefficient at MHC-II presentation due to poor intrinsic protein uptake capability. This resulted in both inferior initiation of T cell responses in the draining lymph node and poor peripheral effector cell accumulation. In addition, TLR stimulation selectively enhanced MHC-II presentation of Ag by dermal DC, but not TIDC in the draining lymph node, and did not affect overall peripheral Ag uptake of either. These results show that TIDC are functionally distinct from normal interstitial DC, thus indicating that neoplastic tissues can evade effector CD4 T cells through modification of DC competence.
Gerner
Michael Y
MY
Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Mescher
Matthew F
MF
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013945:Thymoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen