Antiproliferative effects of interleukin-4 on freshly isolated non-Hodgkin malignant B-lymphoma cells.
The pattern of in vitro growth response of freshly isolated non-Hodgkin malignant lymphoma B cells (NHML) to cytokines was investigated. Ten tumor specimens of low- or intermediate-grade malignancy were selected for study. To assess their proliferative capacity in vitro, B-lymphoma cells were activated through ligation of their surface Ig receptor with insolubilized anti-IgM antibodies or Staphylococcus aureus strain Cowan I (SAC). In the great majority of cases, interleukin-2 (IL-2) was the sole factor that significantly and reproducibly stimulated DNA synthesis in NHML activated through their surface Igs. Other B-cell tropic factors, including IL-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha), failed to elicit a growth response in most of the IL-2-responsive neoplastic samples. However, one specimen among 10 exhibited the opposite pattern of response and proliferated following culture with IL-4 and anti-Ig reagents, but not after IL-2 stimulation. Three specimens could also be induced for DNA synthesis on cross-linking of their surface Igs in the absence of exogenous growth factors. Although IL-4 could not support the in vitro growth of the majority of NHML cases, it strongly suppressed the proliferative signals delivered to these cells by anti-Ig reagents used alone or in combination with IL-2. Our data suggest that, in most cases, IL-4 essentially provides growth-inhibitory signals to NHML when they are activated through their surface Ig receptors and as such may be considered to be a valid candidate for future therapy of this type of mature B-cell malignancy.
Defrance
T
T
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Fluckiger
A C
AC
Rossi
J F
JF
Magaud
J P
JP
Sotto
J J
JJ
Banchereau
J
J
D000888:Antibodies, Anti-Idiotypic; D002455:Cell Division; D016207:Cytokines / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007075:Immunoglobulin M; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015847:Interleukin-4; D004247:DNA