ROLE OF PROLACTIN IN THE IN-VITRO DEVELOPMENT OF INTERLEUKIN-2-DRIVENANTI-TUMORAL LYMPHOKINE-ACTIVATED KILLER-CELLS

Exogenous prolactin (PRL) has been shown to synergize with low-dose in terleukin-2 (IL-2) and induce the proliferation and lymphokine-activat ed killer (LAK) maturation of natural killer (NK) cells. PRL itself ca n also generate LAK activity. Here we show that its local production o ccurs during, and is necessary for, LAK development. IL-2-stimuIated p eripheral blood mononuclear cells (PBMC) and purified NK cells were ex posed to anti-human (h)PRL antiserum, and residual LAK activity was me asured on day 7 against the promyelocytic leukaemia cell line HL-60. I nhibition of LAK activity was much more evident in PBMC compared with NK cell cultures (47% decrease, P = 0.013 and 18.5% decrease, P = 0.04 8, respectively). Up-modulation of a S-32-methionine-labelled 27 000 M W protein was detected in the lysates and supernatants of IL-2-stimula ted PBMC immunoprecipitated with an anti-PRL antiserum. By contrast, t he cytoplasmic PRL immunoreactivity observed in freshly isolated NK ce lls and in IL-2-stimulated, but not unstimulated, NK cell cultures was not associated with PRL gene activation, and can thus be referred to internalized PRL. Preferential re-uptake of externally derived PRL by IL-2-stimulated NK cells was also indicated by up-modulation of the PR L receptor. These data, as a whole, indicate that the PRL promotion of LAK differentiation is mainly mediated by paracrine secretion, with a minor contribution from internalized PRL.