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, 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.
Bianchi
A
A
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Ospedale Molinette, Italy.
Montacchini
L
L
Barral
P
P
Borrione
P
P
Attisano
C
C
Orsini
E
E
Boccadoro
M
M
Pileri
A
A
Massaia
M
M
D001853:Bone Marrow / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D017252:CD3 Complex; D016827:CD8 Antigens; D015847:Interleukin-4