The effect of estradiol (E2) and tamoxifen (TX) on cytotoxic T-lymphocyte (CTL)-mediated target-cell lysis was studied. CTL was generated in mixed cultures of rat spleen cells, using female Fischer 344 rat cells as responders and female Wistar rat cells or Nb2 rat lymphoma cells as stimulators. Concanavalin-Astimulated Wistar lymphoblasts or Nb2 cells were used as targets. CTL harvested on day 5 exerted 1645% cytotoxicity when used at 1:12-1:50 targekeffector cell ratios. Day-6 CTL had no cytotoxic activity. Treatment of target cells with either TX or E2, or both, at I-pM concentrations for 4 hr prior to cytotoxicity testing raised the target-cell killing to loo%. Highly significant enhancement of cytotoxicity was also observed when the drugs were used at 100-, lo-, or I-nM concentrations.Treatment of effector cells under similar conditions led to inhibition of cytotoxicity at I -pM concentration, some enhancement at I00 nM and no effect at 10 and I nM. When treated target and effector cells were combined, the amplification of target-cell lysis was similar in magnitude to that seen in tests with treated targets only. Drug treatment of target cells had no influence on their resistance to lysis in hypotonic solutions or on total and spontaneous release. The inhibition of DNA and protein synthesis in target cells interfered with both basal cytolysis and drug-induced enhancement. The release of the nuclear label, [3H]-thymidine, from Nb2 targets by CTL, was also enhanced by target treatment with TX. These results illustrate that CTL-mediated cytotoxicity is amplified by physiological concentrations (I and 10 nM) of E2 and equimolar concentrations of TX. o 1994 Wiley-Liss, Inc.It is well established that sex hormones influence various features of the immune system, although their mechanism(s) of action has not yet been established with certainty. A direct action on mature lymphoid cells, as well as an indirect action influencing bone-marrow or thymus function, have been proposed as underlying mechanisms. Estradiol is known to enhance humoral immune responses and to suppress cellmediated immunity. The immunological superiority of females and their proneness to autoimmune disease is often attributed to estradiol (Grossman, 1985;Nelson and Steinberg, 1987).The non-steroidal anti-estrogenic agent tamoxifen (TX) is widely applied in the treatment of breast carcinomas and of some other sex-hormone-dependent tumors (Lerner and Jordan, 1990). Although there is considerable evidence to support the hypothesis that this drug inhibits tumor growth by blocking the stimulatory effect of estradiol at the receptor level, there is a good indication that patients with estrogen-receptornegative tumors also benefit from TX treatment (Baral ef al., 1987). The mechanism of inhibition by TX of estrogen-receptornegative tumors is unknown at the present time.Recent studies have revealed that TX is a potent immunomodulatory agent (reviewed by Baral et al., 1994). Therefore, it is possible that immune reactions play a role in the beneficial ef...

After a long period of specialization in science it has been gradually realized that the time has come for coordination, integration and interpretation in Biological Sciences. Advances in Neuroimmune Biology (ANIB) will fulfill, in part, this objective. ANIB deals with the immune-neuroendocrine circuitry as it integrates, coordinates and regulates all biological events in animals and men. This constitutes the Neuroimmune Super system (NISS), the ultimate central regulator of biological processes in animals. Homeostasis is discussed with respect to immune function. The role of the autonomic nervous system, immunological memory, Pavlovian conditioning of immunity, immune deficiency, stress, mast cells and neuroinflammation are included. Therapeutical application of the new knowledge is also considered.