Figure 5. Alefacept increases CD4+ effector memory cell proliferation in vitro.
Nine mixed lymphocyte cultures were incubated for 5 days with Alefacept in 0, 100, and 500ug/mL groups. (A) Increased proliferation (by CFSE decay) was observed in CD3+ cells with increasing doses of Alefacept (p=0.05, normalized at 0ug/mL for variable rates of reactivity among rhesus pairs). (B) CD20+ proliferation was unchanged across different doses of Alefacept. (C) Analysis of memory subsets revealed a proportional increase in CD4+ effector memory cells. CD4+ central memory cells decreased with increasing Alefacept; other subset populations were relatively unchanged. (D) In addition to a proportional increase, CD4+ effector memory cells also had increased proliferation with increasing Alefacept doses. (E) While CD4+ effector memory populations are minimally detected in peripheral blood in vivo, rejected grafts show increased sequestration of CD4+ Tem, suggesting a localized effect that may be difficult to monitor in peripheral blood in vivo.