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Pavan Reddy, Yaping Sun, Tomomi Toubai, Raimon Duran-Struuck, Shawn G. Clouthier, Elizabeth Weisiger, Yoshinobu Maeda, Isao Tawara, Oleg Krijanovski, Erin Gatza, Chen Liu, Chelsea Malter, Paolo Mascagni, Charles A. Dinarello, James L.M. Ferrara
Published in Volume 118, Issue 7
J Clin Invest. 2008; 118(7):2562–2573 doi:10.1172/JCI34712
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Figure 3
HDAC inhibitors regulate in vitro and in vivo functions of DCs.

B6BMDCs were pretreated with diluent or SAHA and used as stimulators in MLR cultures as described in Methods. (A) BALB/c T cell proliferation after 72 h of culture. (B) IL-2 levels in supernatants at 48 h of culture. P = NS, control versus 0.1 μM SAHA. *P < 0.02, **P < 0.01 versus control. (C and D) Addition of (C) anti–TGF-β or (D) anti–IL-10 to SAHA-treated DC cultures did not reverse SAHA-treated DC–mediated suppression. P = NS, SAHA-treated versus control DCs. *P < 0.05 versus control. (E) Naive BALB/c T cells, or those obtained after 48 h of culture with C57BL/6 (B6) DCs pretreated with 0.5 μM SAHA, were restimulated in secondary cultures with control C57BL/6 DCs either separately or together at a 1:1 ratio. T cells cultured from primary SAHA-treated DCs were restimulated with third-party C3H/HeJ BMDCs. P = NS for all between-group comparisons. Data are mean ± SEM of quadruplicate cultures. (F and G) Cd74–/– and HLA-G–/– animals were irradiated and transplanted as described in Methods. Syngeneic (n = 3–4) and some allogeneic animals (n = 4–5) received 4 × 106 to 5 × 106 control B6BMDCs, while some allogeneic recipients (n = 5) received similar numbers of SAHA-treated B6BMDCs, on days –1, 0, and 2 relative to BMT. (F) Donor CD4+ cell number was evaluated in recipients’ spleens on day 7. **P < 0.001 versus allogeneic. Data (mean ± SEM) are from 1 of 3 similar experiments. (G) Donor CD8+ cell number was evaluated in recipients’ spleens on day 21. *P < 0.05 versus allogeneic. Data (mean ± SEM) are from 1 of 2 similar experiments.