Different mechanisms of activation of proliferating CD3+ cells in patients with lymphoproliferative disease of granular lymphocytes.
To investigate the role of p55 and p75 chains of interleukin-2 receptor (IL-2R) on the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), the cells obtained from 11 LDGL patients (belonging to the CD3+ group) were studied for (a) the surface expression and (b) mRNA transcripts of the p55 and p75 IL-2R after activation with anti-CD3 monoclonal antibody (mAb) or interleukin-2 (IL-2). The effects of mAbs specifically blocking the p55 and p75 IL-2R on the generation of proliferative and cytotoxic functions were studied following anti-CD3 mAb stimulation. A significant difference was observed in the expression of p55 and p75 antigens on LDGL cells under resting conditions: a low number of p55 IL-2R+ (mean 1.2 +/- 0.4%) and high values of p75 IL-2R+ cells (54.9 +/- 7.4%). Accordingly, a barely detectable message for the p55 IL-2R and a strong signal for the p75 IL-2R mRNA were demonstrated. Following activation with anti-CD3 or IL-2, different patterns of IL-2R expression were observed. Anti-CD3 mAb induced an increase in the expression of the p55 IL-2R both at the mRNA and antigen level, whereas the p75 values remained consistently raised. In contrast, IL-2 induced the expression of p55 IL-2R mRNA associated with only a slight expression of this antigen. This finding was associated with a decrease in the cell expression of the p75 IL-2R, whereas the amount of p75 mRNA was unchanged. Both anti-CD3 mAb and IL-2 induced cell proliferation and cytotoxicity against the K-562 target cells. Anti-p55 IL-2R mAb did not affect the cytotoxic activity mediated by anti-CD3, but it markedly inhibited cell proliferation. Anti-p75 mAb did not inhibit either lytic function or cell proliferation mediated by anti-CD3 mAb, suggesting that only the high affinity IL-2R (p55 plus p75) is involved in anti-CD3 mediated cell activation in LDGL patients. This mechanism is different from that responsible for the IL-2 activation of CD3+ GL in LDGL patients, which is achieved through the p75 IL-2R alone. These results provide new insights into the pathophysiology of proliferating GL in LDGL patients and may also contribute to further characterization of the normal CD3+ GL population.
Zambello
R
R
Department of Clinical Medicine, University of Padua, Italy.
Cassatella
M A
MA
Trentin
L
L
Bulian
P
P
Siviero
F
F
Feruglio
C
C
Agostini
C
C
Vespignani
M
M
Chisesi
T
T
Pizzolo
G
G
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015152:Blotting, Northern; D017252:CD3 Complex; D002469:Cell Separation; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2