CD83 expression on dendritic cells and T cells: correlation with effective immune responses.
Human CD83 is a marker molecule for mature dendritic cells (DC) and is also expressed on activated B and T cells. Although CD83 has been implicated in immune responses, its function on DC and T cells remains unclear. In this study, we wanted to assess the role of CD83 expressed on DC and T cells in the immune response. Down-regulation of CD83 expression on human DC through RNA interference (RNAi) results in a less potent induction of allogeneic T cell proliferation, reduced IFN-gamma secretion by established T cells and decreased capacity in the priming of functional tumor antigen-specific CD8+ T lymphocytes. In addition, CD83 mRNA-electroporated DC are stronger T cell stimulators. However, CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC. Co-culture of immature DC with TIL or K562 cells overexpressing CD83 results in the production of enhanced levels of pro-inflammatory cytokines, whereas this production is less pronounced or even absent in co-cultures with non-modified TIL or K562 cells. In conclusion, we demonstrate that CD83 expression on T cells and DC modulates the immune response by activating DC and by delivering costimulatory signals for the stimulation of naive and memory T cells, respectively.
Aerts-Toegaert
Cindy
C
Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Brussels, Belgium.
Heirman
Carlo
C
Tuyaerts
Sandra
S
Corthals
Jurgen
J
Aerts
Joeri L
JL
Bonehill
Aude
A
Thielemans
Kris
K
Breckpot
Karine
K
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics*; D020014:K562 Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen