Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo
- The Rockefeller University, United States
- Hospital for Special Surgery, United States
- Howard Hughes Medical Institute, The Rockefeller University, United States
- Memorial Sloan-Kettering Cancer Center, United States
Figures
Figure 1
FK506 treated DC secrete a direct T cell inhibitor.
(A) T cell proliferative responses to allogeneic DC or FKDC after 5-day coculture. DC wash control indicates untreated DCs suspended in supernatant of the last wash of FKDC. Data are mean counts per …
Figure 2
FK506 derived from FK506 treated DC blocks T cell activation.
(A) Transcription, translation and translocation through the secretory pathway are not required for FKDC to produce a T cell inhibitor. DC were pretreated with actinomycin, emetine, brefeldin A or …
Figure 3
FK506 derived from FK506 treated DC causes activated T cell death in vitro.
(A) Annexin V stained CFSE labeled allogeneic CD4+ T cells cultured with DC or FKDC ± IL2 for 4 days. Boxes indicate gating strategy for selecting undivided or divided T cells in Figure 3B and C. (B)…
Figure 4
FK506 treated DC modulate antigen specific immune responses in vivo.
(A) DBA1/J bone marrow derived DC pulsed with either type I or II collagen and treated with FK506 or media. DC were transferred intravenously 7 and 14 days after type II collagen/CFA immunization. …
Author response image 1
FK506 delivered by DCs protects from systemic immunosuppression.
CD4+ splenocytes from an untreated mouse were cultured with serum drawn from the indicated groups of mice after last dose of either treatment regimen, and the CD4+ T cells were then stimulated for 4 …
Author response image 2
FK506 delivered by DCs protects from off-target organ toxicity.
Serum amylase drawn from the indicated groups of mice after last dose of either treatment regimen, as described in Author response image 1. N = 6–10 mice per group. Gray circles are serum amylase …
Author response image 3
Effect of Rapamycin and FK506 on DC.
Mature monocyte derived DCs were treated with 0.5 μM Rapamycin or media control for 18 hours prior to treatment with 0.5 μM FK506 or media control for one hour and washed extensively. Syngeneic CD4+ …
Tables
Table 1
Mature, monocyte derived DC express mRNA of several FKBP
| Accession number | Gene name | Mean affymetrix expression level | Standard deviation |
| NM_000801.1 | FK506-binding protein 1A (12kD) (FKBP1A) | 1210.0 | 178.4 |
| NM_004470.1 | FK506-binding protein 2 (13kD) (FKBP2) | 370.8 | 23.7 |
| NM_003602.1 | FK506-binding protein 6 (36kD) (FKBP6) | 289.0 | 51.1 |
| NM_012181.1 | FK506-binding protein 8 (38kD) (FKBP8) | 211.8 | 82.9 |
| NM_004117.1 | FK506-binding protein 5 (FKBP5) | 203.6 | 40.8 |
| NM_002014.1 | FK506-binding protein 4 (59kD) (FKBP4) | 121.8 | 47.1 |
| NM_002013.1 | FK506-binding protein 3 (25kD) (FKBP3) | 116.5 | 21.2 |
| AF322070.1 | FK506-binding protein FKBP9 | 115.6 | 11.6 |
| NM_004116.1 | FK506-binding protein 1B (12.6 kD) (FKBP1B) | 90.7 | 25.3 |
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FK506 binding proteins expressed in mature human DCs are ranked by mean Affymetrix expression level; values over 200 are considered to be robustly present. Mean expression and standard deviation are derived from four biologic replicates.
