Sirt-1 modulates T- and B-cell activation in cGVHD. Lethally irradiated (700 cGy) BALB/c mice underwent transplantation with 5 × 106 TCD-BM alone or plus 5 × 105 CD25− splenocytes per mouse isolated from WT or Sirt-1−/− donors. (A) Body weight loss. (B) cGVHD clinical and (C) pathology scores. (D) Representative pictures of skin and large intestine biopsies stained with hematoxylin and eosin (original magnification ×200). (E) Foxp3 expression on gated donor CD4 in spleen and frequency of follicular Treg cells (Foxp3+CXCR5+PD-1+) and Tfh (Foxp3−CXCR5+PD-1+) were determined on day 60. (F) IFN-γ expression was shown on gated donor CD4 and CD8 T cells. (G) Splenic B cells were analyzed for B220+, B220−CD138+, and (H) activation markers, CD86 and MHCII. Data were combined from 2 independent experiments (n = 6-10 mice/group). Log-rank (Mantel-Cox) test was used to analyze body weight, and Student t test was used for statistical analysis. *P < .05; **P < .01; ***P < .001; ****P < .0001.