CD3-INDUCED T-CELL ACTIVATION IN THE BONE-MARROW OF MYELOMA PATIENTS - MAJOR ROLE OF CD4(+) CELLS

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, CD45RO 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.