Figure 1

Alloreactive CD8 T cells are resistant to ABT-737 after DST. (a) Characterization of the BM3.3 model; after 48 h of MLR with BM3.3 responders and CD8-depleted B6 stimulators, all responder (Ti98+) CD8 T cells were activated, as measured by CD25 expression in FACS. (b) Experimental setup: synchimeric mice were generated by bone marrow (BM) transplantation from BM3.3 mice into CBA recipients after non-lethal total body irradiation (3 Gy). After 6 weeks, synchimeras expressed the BM3.3 TCR (Ti98+) on about 6% of the whole CD8-positive population. The mice were primed by i.v. injection of B6 splenocytes, and 2 days later, treatment with ABT-737 was started. (c and d) Exposure to ABT-737 induced a relative and absolute reduction of CD3+ cells in peripheral blood, and similarly affected CD4+ and CD8+ T cells. (e) The increase of the percentage of Ti98+ cells among CD8 T cells was significantly higher in mice exposed to ABT-737 (P<0.01). Statistical comparison of data registered at baseline and at day 5 by paired t-test; *P<0.05, **P<0.01; n=5. Representative results of one of two independent experiments are shown