Independent and synergistic effect of interleukin-2 and prolactin on development of T- and NK-derived LAK effectors.
We have studied the effect of recombinant (r)-Prl on the in vitro-induced MHC-unrestricted cytotoxicity of NK and T cells. A 4-day treatment with r-Prl in serum-free medium enhanced the cytotoxicity of NK cells to the NK-susceptible cell lines K562 and U937, but did not induce de novo NK cytotoxicity in T lymphocytes. By contrast, development of cytotoxicity against the LAK-susceptible cell lines HL60, Jurkat, Daudi and Supt-1 occurred in both NK and T cells. The effect of r-Prl on NK cells was bi-phasic with peaks at 25 ng/ml (1.2 nM), the upper physiological level, and 200 ng/ml (9.6 nM). By contrast, LAK activation of T cells only occurred at the highest r-Prl concentration. In addition to its intrinsic stimulatory activity, r-Prl was also capable of modulating in a dose-dependent manner distinct stages of the IL2-driven LAK/T differentiation pathway. Physiological concentrations of r-Prl interacted with low doses r-IL2 to significantly enhance generation of NK- and T-LAK activities. By contrast, pathological concentrations had opposite effects on generation of optimal LAK response, depending on the kind of LAK progenitor. The T-derived LAK activity was reversibly inhibited at the effector level, while the mature NK-LAK cells were stimulated. These data confirm our previous findings of a co-operative effect of Prl and IL2 on NK cell proliferation and reinforce the view that the signals conveyed by the two factors may be functionally related.
Cesano
A
A
Istituto di Medicina Interna, Università di Torino, Italy.
Oberholtzer
E
E
Contarini
M
M
Geuna
M
M
Bellone
G
G
Matera
L
L
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects*; D011388:Prolactin / Q000494:pharmacology*; D017452:Receptors, IgG / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
D007376:Interleukin-2; D017452:Receptors, IgG; D011388:Prolactin; D003165:Complement System Proteins