Repopulation of memory T cells (Tmem) in allograft recipients after lymphodepletion is a major barrier to transplant tolerance induction. Ineffective depletion of naïve T cells (Tn) and Tmem may predispose to repopulation of Tmem after transplantation. Cynomolgus macaque monkeys given heart allografts were lymphodepleted using Alemtuzumab (Campath-1H; anti-CD52). Peripheral blood (PB) and lymph nodes (LN) were analyzed for CD95- (Tn) and CD95+ cells (Tmem), one day, one month and up to three months after Alemtuzumab infusion. CD52 expression, susceptibility to Alemtuzumab cytotoxicity and pro-apoptotic caspase-3 were evaluated in Tn and Tmem. In vivo, Alemtuzumab induction profoundly depleted lymphocytes in PB (99% reduction) but exerted a lesser effect in LN (70% reduction), with similar depletion of Tn and Tmem subsets. After transplantation, Tmem comprised the majority of lymphocytes in PB and LN. In vitro, LN T cells were more resistant to Alemtuzumab-mediated cytotoxicity than PB lymphocytes. CD4+ Tn and Tmem were equally susceptible to Alemtuzumab-mediated cytotoxicity, whereas CD8+ Tn were more resistant than CD8+ Tmem. However, no significant differences in CD52 expression between lymphocyte subsets in PB and LN were observed. Caspase-3 expression was higher in PB than LN T cells. CD4+ and CD8+ Tn expressed lower levels of Caspase-3 than Tmem, in both PB and LN. Thus, after Alemtuzumab infusion, residual Tn in secondary lymphoid tissue may predispose to rapid recovery of Tmem in allograft recipients.

Alemtuzumab, Lymph node, Memory T cell, Naïve T cell, Non-human primate, Transplantation
dx.doi.org/10.1016/j.trim.2013.10.002, hdl.handle.net/1765/65450
Transplant Immunology
Department of Surgery

Marco, J, Dons, E.M, van der Windt, D.J, Bhama, J.K, Lu, L.T, Zahorchak, A.F, … Thomson, A.W. (2013). Post-transplant repopulation of naïve and memory T cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys. Transplant Immunology, 29(1-4), 88–98. doi:10.1016/j.trim.2013.10.002