INDEPENDENT AND SYNERGISTIC EFFECT OF INTERLEUKIN-2 AND PROLACTIN ON DEVELOPMENT OF T-DERIVED AND NK-DERIVED LAK EFFECTORS

We have studied the effect of recombinant (r)-Prl on the in vitro-indu ced 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 cy totoxicity 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 phisiol ogical 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 t o its intrinsic stimulatory activity, r-Prl was also capable of modula ting in a dose-dependent manner distinct stages of the IL2-driven LAK/ T differentiation pathway. Physiological concentrations of r-Prl inter acted with low doses r-IL2 to significantly enhance generation of NK-a nd T-LAK activities. By contrast, pathological concentrations had oppo site effects on generation of optimal LAK response, depending on the k ind of LAK progenitor. The T-derived LAK activity was reversibly inhib ited at the effector level, while the mature NK-LAK cells were stimula ted. These data confirm our previous findings of a co-operative effect of Prl and IL2 on NK cell proliferation and reinforce the view that t he signals conveyed by the two factors may be functionally related.