Figure 1.
TLI/ATS/CTX overcomes engraftment and GVHD barriers following MHC-mismatched allogeneic BMT for β-thal. (A) Experimental design for TLI/ATS and TLI/ATS/CTX conditioning. Representative image (top right) of recipient mouse in lead shielding jig delineates TLI-exposed regions. Main monitored parameters in recipients of BMT from day 0 to day 100 are indicated in the text box. BMT = 50 × 106 BM + 60 × 106 spleen cells from WT BALB/c (H-2d) donors. CBC, complete blood count. (B) Mean ± standard error of the mean (SEM) donor chimerism (%) at day 28 (D28) and day 100 (D100) measured by FACS analysis of gated live subsets (TCRαβ+, B220+, Gr-1/Ly6+, CD11b/Mac-1+) in peripheral blood of WT and β-thal+/− HW-80 recipients of TLI/ATS/CTX or TLI/ATS conditioning and WT BALB/c BMT. P values given are between TLI/ATS/CTX and TLI/ATS treatment within WT or β-thalassemic (β-thal+/−) recipient groups indicated. (C) Kaplan-Meier analysis of cumulative survival (%) of WT and β-thal+/− HW-80 recipients of TLI/ATS/CTX or TLI/ATS conditioning and WT BALB/c BMT. Data are cumulative (n = 8 experiments). (D) Mean ± SEM body mass (grams) of mice engrafting by day 28 (includes those rejecting the donor graft by D100) in experimental groups shown in C. Data are cumulative (n = 8 experiments). (E) Mean ± SEM cumulative GVHD scores (left) and colon GVHD scores (right) of engrafting WT and β-thal+/−HW-80 recipients of TLI/ATS/CTX or TLI/ATS conditioning and WT BALB/c BMT. Data are cumulative (n = 8 experiments). *Mean score, 0.