title: Recipient memory-like lymphocytes remain unresponsive to graft antigens after CAMPATH-1H induction with reduced maintenance immunosuppression.
abstract: BACKGROUND
  Treatment with CAMPATH-1H at the time of transplantation allows reduced maintenance immunosuppression. We hypothesized that CAMPATH-1H induction would modulate the response of repopulating leukocytes to donor alloantigens.
  
  
  METHODS
  The phenotype, proliferative and stimulatory capacity of peripheral blood leukocytes from 14 renal transplant recipients treated with CAMPATH-1H and reduced immunosuppression with mycophenolate mofetil and tacrolimus were investigated for the first six months after transplantation. The impact of immunosuppressive drugs on leukocytes that escape depletion was also evaluated in vitro.
  
  
  RESULTS
  CAMPATH-1H therapy caused a significant decrease in the number of B and T cells, with CD4 T central memory cells being the most resistant to depletion. The recovery of CD8 T cells was faster than that of CD4 T cells. Lymphopenia correlated with a decrease in both proliferative and effector responses, however, the recipient T cells remained responsive to third-party antigens. Dendritic cells (DC) were also depleted but to a lesser extent than lymphocytes; lymphoid DC were more resistant than myeloid DC; these changes correlated with decreased allostimulatory capacity. One of the patients experienced rejection that was treated successfully. The rejection was associated with a high proportion of CD4 T effector memory cells and myeloid DC, increased proliferation and enhanced effector activity to donor antigens. In vitro studies confirmed that the reduced dose of immunosuppressive drugs used could prevent activated T cells from switching to the effector compartment, suppressing both their proliferation and effector activity.
  
  
  CONCLUSIONS
  CAMPATH-1H induction combined with reduced maintenance immunosuppression is sufficient to control the effector phase of immune response to donor antigens.
authors.affiliation: Transplantation Research Immunology Group and Oxford Transplant Centre, Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: Miguel
authors.initials: M
authors.lastname: Zilvetti
authors.forename: Peter
authors.initials: P
authors.lastname: Friend
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007258:Informed Consent; D007371:Interferon-gamma / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D007371:Interferon-gamma