CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells

Br J Haematol. 1995 Jul;90(3):625-32. doi: 10.1111/j.1365-2141.1995.tb05594.x.

Abstract

A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / immunology*
  • CD3 Complex / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8 Antigens / immunology
  • Humans
  • Immunophenotyping
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / immunology
  • Multiple Myeloma / immunology*
  • T-Lymphocyte Subsets / immunology

Substances

  • CD3 Complex
  • CD8 Antigens
  • Interleukin-4