Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression.
We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 (B7) molecules on dendritic cells (DCs) in vitro. In this report we show that the extent of down-modulation is functionally significant because Treg-cell conditioned DCs induced poor T-cell proliferation responses. Further, we report that down-modulation was induced rapidly and was inhibited by blocking cytotoxic T lymphocyte antigen-4 (CTLA-4), which is constitutively expressed by the Treg cells. Even though Treg cells have previously been reported to kill antigen-presenting cells, the down-modulation was not due to selective killing of DCs expressing high level of the costimulatory molecules. We propose that Treg cells down-modulate B7-molecules on DCs in a CTLA-4-dependent way, thereby enhancing suppression of T-cell activity.
Oderup
Cecilia
C
Immunology Unit, BMC I:13, Department of Experimental Medical Research, Lund University, Lund, Sweden.
Cederbom
Lukas
L
Makowska
Anna
A
Cilio
Corrado M
CM
Ivars
Fredrik
F
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D015375:Receptors, Interleukin-2