Quantitation of T cell depletion by limiting dilution analysis

Haematologica. 1991 May-Jun;76(3):188-92.

Abstract

Background: We evaluated a culture method for enumeration of residual T cells remaining in marrow after treatment with antibody and complement or with immunotoxin.

Methods: Marrow cells were cultured at limiting dilutions with phytohemagglutinin in the presence of Epstein Barr virus transformed human lymphoblastoid cells, and supernates were tested three days later for IL-2 by a cell proliferation assay. This method provides a simple, reliable, objective and rapid enumeration of T cells in marrow before and after treatment.

Results: Approximately 6% of untreated marrow mononuclear cells can produce IL-2 in such clonal cultures. Treatment with antibodies and complement under conditions identical to those used for our previous clinical trials produced a 3.7 log depletion of IL-2 precursors, whereas treatment with a ricin A chain anti-CD3 immunotoxin produced a 3.0 log depletion.

Conclusions: Clinical correlations are in progress for assessing whether T cell depletion evaluated with the present method equals previous techniques. The extreme depletion of T cells accomplished by these methods may partly account for the high graft failure rate seen in our clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Bone Marrow Cells*
  • CD3 Complex
  • Cell Line, Transformed
  • Cells, Cultured
  • Complement System Proteins
  • Herpesvirus 4, Human
  • Humans
  • Immunotoxins
  • Interleukin-2 / analysis*
  • Leukocyte Count / methods*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Depletion* / methods
  • Phytohemagglutinins
  • Receptors, Antigen, T-Cell / immunology
  • Ricin
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Immunotoxins
  • Interleukin-2
  • Phytohemagglutinins
  • Receptors, Antigen, T-Cell
  • Complement System Proteins
  • Ricin