Prolactin receptors on large granular lymphocytes: dual regulation by cyclosporin A

Although evidence has been provided for a modulatory role of prolactin (PRL) on humoral and cell-mediated immune responses and PRL receptors have been found on T and B lymphocytes, no indications exist concerning the influence of PRL on natural killer (NK) activity nor has a structural basis for interaction been found on the NK effector cells (large granular lymphocytes, LGL). We show here that highly purified LGL express binding sites for PRL. The calculated receptor number was 660 per cell and the dissociation constant (Kd) was 3.0 X 10(-10) M. Since previous studies have reported that cyclosporin (CsA), an immunosuppressive agent used in organ transplant patients, affects the binding of PRL to T and B lymphocytes, but not to rabbit mammary gland cells, we investigated whether this compound could alter the binding of the hormone to LGL. At concentrations from 10(-7) to 10(-6), corresponding to the therapeutical range, CsA induced a complete inhibition of the PRL binding. By contrast, concentrations of CsA ranging from 10(-11) to 10(-9) increased the PRL binding to more than 100% of control levels. In addition to their antitumor role, LGL have been proposed to participate in graft versus host disease and in transplant rejection. The finding that CsA can differently affect PRL-receptor expression on LGL points to an involvement of CsA--PRL interactions in determining the output of these immune responses. In addition, these data strongly support the idea of a close relationship between the neuroendocrine and immune systems.