Release of interleukin-2-like material by B-chronic lymphocytic leukemia cells. An autocrine or paracrine model of production and utilization?
In a series of untreated patients with B-cell chronic lymphocytic leukemia (B-CLL), the capacity of the neoplastic B-cell population to release an interleukin-2 like factor (IL-2lf) was assessed. While unstimulated purified leukemic B-cells showed no IL-2lf production, in 16 of the 27 cases tested (59.2%) significant amounts of IL-2lf (4.3-125 U) were released following activation with phytohemagglutinin (PHA) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In seven further cases (25.9%), small quantities of IL-2lf (0.2-1.7 U) were detected, while only in four (14.8%) no release was found. In 11 of the 20 cases (55%), PHA alone was also capable of inducing the production of limited amounts of IL-2lf (0.4-8 U). Only small amounts were released from B lymphocytes isolated from normal tonsils both with PHA and PHA plus TPA. Further purification using a fluorescence activated cell sorter suggests that the IL-2lf is truly produced by leukemic B cells and blocking experiments with the PC-61 monoclonal antibody indicate that IL-2lf and IL-2 use the same cell membrane receptor. However, co-cultures of leukemic B cells with small amounts of autologous or allogeneic T lymphocytes enhanced the amount of IL-2lf released into the supernatant to values markedly higher than those released by T- or B cells alone. Unlike normal B lymphocytes, unstimulated purified leukemic B cells from 17 out of 23 B-CLL cases (73.9%) were capable of absorbing variable amounts of exogenous IL-2. In addition, in six of the 11 cases tested (54.5%) IL-2 alone was capable of producing a 2-4 fold increase of thymidine uptake. In six out of eight cases (75%), a 2-5 fold enhancement of the proliferative response was observed when the leukemic B cells were co-stimulated with Staphylococcus aureus Cowan 1 (SAC) and IL-2. Moreover, when the cells were pre-activated with SAC or with PHA plus TPA and then further stimulated with IL-2, a 2-20 fold increase in proliferative response was found in the majority of cases studied. These findings indicate that elevated quantities of IL-2lf may be released in B-CLL particularly due to the B- and T cell interconnections, and that the leukemic B cells appear capable of absorbing IL-2 and of proliferating after costimulation with IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)
Giovarelli
M
M
Istituto di Microbiologia, University of Torino, Italy.
Foa
R
R
Benetton
G
G
Lusso
P
P
Fierro
M T
MT
Forni
G
G
D000911:Antibodies, Monoclonal / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002469:Cell Separation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008954:Models, Biological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2