Effect of different induction strategies on effector, regulatory and memory lymphocyte sub‐populations in clinical islet transplantation

• Published in: Transplant international Vol. 22; no. 2; pp. 182 - 191
• Main Authors: Toso, Christian, Edgar, Ryan, Pawlick, Rena, Emamaullee, Juliet, Merani, Shaheed, Dinyari, Parastoo, Mueller, Thomas F., Shapiro, A. M. James, Anderson, Colin C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2009
• Subjects: Alemtuzumab; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - pharmacology; Antilymphocyte Serum; CD4 antigen; Female; Flow Cytometry; Humans; Immune status; Immunoglobulin G - pharmacology; Immunological memory; Immunosuppression; Immunosuppressive Agents - pharmacology; islet; Islet cells; Islets of Langerhans Transplantation - immunology; lymphocyte; Lymphocyte Subsets - drug effects; Lymphocyte Subsets - immunology; Lymphocytes B; Lymphocytes T; Male; memory; Memory cells; Middle Aged; Monoclonal antibodies; Pancreatic islet transplantation; Peripheral blood; Prospective Studies; regulatory; thymoglobulin; Transplantation
• ISSN: 0934-0874; 1432-2277
• DOI: 10.1111/j.1432-2277.2008.00746.x

Summary This prospective study assessed lymphocyte subsets in the peripheral blood of 42 islet allograft recipients using flow cytometry from 2 weeks and up to 2 years post‐transplantation. Subjects received daclizumab (n = 16), Thymoglobulin (n = 12) or alemtuzumab (n = 14). Alemtuzumab was associated with an early (within 1 month) and transient (up to 6 months) increase in the frequency of CD3+ CD4+ Foxp3+ T cells, while daclizumab induced a near complete loss of these cells (P ≤ 0.001). The frequency of memory CD4+ T cells was increased following depleting immunosuppression induction with either Thymoglobulin or alemtuzumab (P ≤ 0.05), but remained unchanged while using daclizumab. Alemtuzumab induction resulted in a significant loss of memory B lymphocytes when compared with the other induction groups (P ≤ 0.001). While the clinical significance of these findings remains to be fully determined, the observed altered balance between effector, regulatory and memory cells suggests that the immune status of patients will be affected according to the induction strategy chosen.