Cytotoxic difference of T cells expanded with anti-CD3 monoclonal antibody in the presence and absence of anti-CD 28 monoclonal antibody.
Bulk T cells can be expanded by CD3 stimulation alone (CD3-Ts) or by CD3/CD28 dual stimulation (CD3/CD28-Ts) of peripheral blood mononuclear cells (PBMC). However, few reports have described the difference of features between CD3-Ts and CD3/CD28-Ts. PBMC were stimulated with anti-CD3 monoclonal antibody (mAb) alone or co-stimulated with anti-CD3/CD28 mAbs immobilized on plastic plates, in the presence of rhIL-2 for 4 days, subsequently cultured in the presence of rhIL-2 with no antibody then analyzed. The expansion rate was significantly lower for CD3-Ts (965 + 510-fold, n=5) than CD3/CD28-Ts (2263 + 856-fold, n=5) (p<0.05). The CD4/CD8 ratio, the percentage of CD28(+) cell, and the percentage of T cells with no ability to generate intracytoplasmic interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) were all significantly higher, but, phenotypically, memory cells were lower in CD3/CD28-Ts than in CD3-Ts. The levels of activity of both natural killer (NK) and lymphocyte-activated killer (LAK) cells were lower in CD3/CD28-Ts than CD3-Ts. In comparison to CD3-Ts, CD3/CD28-Ts showed impaired migration toward RANTES. In conclusion, T cells expanded with anti-CD3 and anti-CD28 mAbs differ from those expanded with anti-CD3 alone with proliferation, cytotoxicity, chemotaxis, and phenotype. These differences may exert profound influences on the therapeutic potential of output cells.
Yamada-Ohnishi
Yoshiko
Y
Hokkaido Red Cross Blood Center, Sapporo 063-0002, Japan.
Azuma
Hiroshi
H
Urushibara
Noriko
N
Yamaguchi
Miki
M
Fujihara
Mitsuhiro
M
Kobata
Tetsuji
T
Ikeda
Hisami
H
D018033:Antibodies, Bispecific / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin