Phenotypic and functional modulation of interleukin-2-activated peripheral blood mononuclear cells by anti-CD3 and anti-CD28 antibody.
For effective adoptive cancer immunotherapy, not only killer lymphocytes (cytotoxic T cells or NK cells) but also helper T cells are considered to be beneficial. The conventional culture of human lymphocytes with high-dose of recombinant interleukin -2 (rIL-2) yields a high proportion of killer cells (CD8+ or CD56+ cells) but is usually accompanied by a decrease in the proportion of CD4+ cells. Peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 monoclonal antibody (10 ng/ml) in the absence of rIL-2 during the initial 48-hr period of cultivation followed by the addition of rIL-2 (200 Japan reference units/ml) (referred to as anti-CD3-rIL-2) resulted in CD4+ cells expanding 8.0- to 63.3-fold at day 12-14. When PBMC were cultivated with rIL-2 alone, or with rIL-2 together with anti-CD3 initially, CD4+ cells expanded 1.7-6.2- or 5.7-36.9-fold, respectively. The expansion of CD4+ cells from PBMC in the anti-CD3-rIL-2 cultures was enhanced by the addition of anti-CD28 monoclonal antibody at the initiation of cultures (500 ng/ml) (referred to as anti-CD3/anti-CD28-rIL-2) (12.1- to 127.8-fold expansion). The anti-CD3-rIL-2 and anti-CD3/anti-CD28-rIL-2 cultures also demonstrated a lesser expansion of CD3-CD56+ cells (NK cells). The PBMC in the anti-CD3/anti-CD28-rIL-2 cultures showed low cytotoxic activity per cell; however, the cytotoxic activity per total culture was comparable to that of PBMC expanded with rIL-2 alone because of the larger total expansion of the former culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshino
I
I
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yano
T
T
Miyamoto
M
M
Sugimachi
K
K
Kimura
G
G
Nomoto
K
K
D000199:Actins / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D000199:Actins; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D017931:DNA Primers; D007376:Interleukin-2; D007377:Interleukin-3; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma