The most important progress in immunology in the last decade is the description of regulatory lymphocytes, among which Treg cells and regulatory NKT cells are much attractive to not only immunologists but also almost all biomedical researchers. Meanwhile, it is noted that NK cells are not only ＂Killers＂ but also regulate innate and adaptive immunity, especially in early stage, by secreting cytokines and cell-cell contact. In this review, we are going to briefly summarize the progresses in regulatory lymphocytes including T cells （Treg, Tr1, Th3）, NKT cells and NK cells, and then extensively introduce the positive regulatory function of NK cells in both normal immune response and in disease condition （tumor, infection and autoimmunity）, and finally, to focus on the most latest progression in the negative regulatory effects of NK cells on normal and pathogenic immune response. In conclusion, we speculate that a ＂regulatory NK （NK-reg）＂ cell subset exist and need to explore.
We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.
Partial hepatectomy （PHx） in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins （HSPs） were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration. Cellular ＆ Molecular Immunology. 2007;4（1）：53-57.
Recombinant human prolactin(rhPRL)was administered to huPBL-SCID mice to determine its effects on human immunologic reconstitution and function.The huPBL-SCID mice were given 10 μg i.p.injection of rhPRL every other day for a total of 10 injections after huPBL were transfered.The results demonstrated that rhPRL improved the engraftment of lymphocytes into thymus,lymph nodes and spleens,showing that the cellularities of these organs increased although the cellularities tended to vary depending on the donor.The amounts of human T cells(HLA-ABC^+/CD3^+)increased greatly in thymus(14.2 folds),spleen(4.16 folds)and lymph nodes(40.18 folds)after rhPRL injections.The amounts of human B cells(HLA-ABC^+/CD19^+)also increased greatly in lymph nodes(42.5 folds)and spleen(5.78 folds).The lymph node cells from the rhPRL-treated huPBL-SCID mice were more sensitive to PHA stimulation([~3H]thymidine incorporation).The supernatant of PHA-stimulated PBL from rhPRL-treated huPBL/SCID chimerism contained more cytokines (IFN-γ and IL-2).The natural cytotoxicity against human sensitive target cells,K562 cells,from spleen and bone marrow of hPBL/SCID chimerism was significantly enhanced by rhPRL administration.The lymph node cells were stimulated with LPS in vitro for 3 days and the lymphocytes from the rhPRL-treated huPBL-SCID mice were more sensitive to mitogen stimulation.Both serum total IgG level and IgM level of rhPRL-treated huPBL/SCID chimerism were increased,and even without DT-rechallenge the base line of DT-specific IgG was elevated after rhPRL treatment in huPBL-SCID mice.Thus,rhPRL stimulation promotes reconstitution of human immune system in huPBL-SCID mice.Cellular & Molecular Immunology.2004;1(2):129-136.
