Different mechanisms of Campath-1H-mediated depletion for CD4 and CD8 T cells in peripheral blood

Transpl Int. 2006 Nov;19(11):927-36. doi: 10.1111/j.1432-2277.2006.00382.x.

Abstract

It is assumed that complement and noncomplement-mediated mechanisms are similarly responsible for Campath-1H-mediated killing of all T-cell subtypes in vivo. However, the differing surface expression of CD52 on T-cell subtypes suggests that may not be the case. The purpose of this study is to determine the extent and mechanism of Campath-1H-mediated elimination of different T-cell subtypes in peripheral blood. Whole blood or lymphocytes isolated from peripheral blood of healthy volunteers by Ficoll density centrifugation were incubated with Campath-1H, with or without complement and/or serum, and the resultant T-cell elimination mechanisms studied. For CD4(+) T lymphocytes, 60% and 40% cell death and for CD8(+) T lymphocytes 23% and 77% cell death, in peripheral blood, was mediated by complement and noncomplement mediated mechanisms, respectively. CD4(+) T cells demonstrated approximately twice the amount of surface CD52 compared with CD8(+) T cells, consistent with primarily complement-mediated killing for CD4(+) T cells. Thus, peripheral blood supports differential and partial elimination of T-cell subtypes, suggesting that the complete T-cell elimination seen in transplant recipients is most likely due to contribution from other lymphoid organs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab
  • Ammonium Chloride / pharmacology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / pharmacology*
  • Antigens, CD / biosynthesis
  • Antigens, Neoplasm / biosynthesis
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD52 Antigen
  • CD8-Positive T-Lymphocytes / drug effects*
  • Cell Death
  • Cell Separation
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Glycoproteins / biosynthesis
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocytes / metabolism
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Antigens, CD
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • Immunosuppressive Agents
  • Ammonium Chloride
  • Alemtuzumab