Lymphocyte depletion and repopulation in peripheral blood and small intestine of cynomolgus monkeys after alemtuzumab treatment

Abstract

Background: Alemtuzumab has been used as an induction agent in organ transplantation over 10 years, but the effect of alemtuzumab on lymphocytes in small intestine was not clear. We investigate lymphocyte depletion and repopulation phenomena both in peripheral blood and small intestine of cynomolgus monkeys, to assess the model using in preclinical transplantation.

Materials and methods: Monkeys without CD52 antigen on erythrocytes were selected. Lymphocyte depletion and repopulation was documented by flow cytometry. Sections of ileum were obtained for isolation of intestinal intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), and also for immunofluorescence examination.

Results: Powerful depletion of lymphocytes (>80%) from blood followed by gradual repopulation was observed. CD20(+) B cells, CD8(+) T cells, CD4(+) T cells returned to pretreatment levels by d 21, 35, 56. IEL, LPL reduced by 70%, 72% on d 9, recovered to 59%, 57% of pretreatment levels by d 35, and were completed by d 56. Depletion and repopulation of IEL and LPL were confirmed by immunofluorescence.

Conclusions: Depletion of lymphocytes in peripheral blood was less powerful and repopulation occurred faster than in patients. The lymphocyte depletion and repopulation occurred in small intestine. This model can be used in preclinical transplantation.