ABSTRACT
Vaccination during periods of lymphopenia may facilitate immune responses to weak self-antigens and enhance antitumor immunity. The objective of this study was to determine the effectiveness of tumor vaccine immunotherapy combined with immune reconstruction using tumor-bearing host immune cells in lymphopenia, and to investigate the role of tumor-bearing host T cells activated in vitro during immunotherapy. Animal study conducted in the First Affiliated Hospital of Xi'an Jiaotong University from January 2009 to January 2010. Lymphopenia was induced by cyclophosphamide. A reconstituted immune system with different syngeneic lymphocytes was employed, including lymphocytes from naive rats [unsensitized group], tumor-bearing rats [tumor-bearing group], and tumor-bearing rats activated in vitro [activated group]. All rats were immunized with granulocyte-macrophage colony-stimulating factor [GM-CSF]-modified NuTu-19 ovarian cancer [GM-CSF/NuTu-19] cells. Tumor vaccine-draining lymph nodes [TVDLNs] were harvested, and then stimulated to induce effector T cells [T[E]]. T[E] were then adoptively transferred to rats bearing a 3-day pre-established abdominal tumor [NuTu-19], and the survival rate was calculated. Compared with the unsensitized group, the levels of interleukin-2 [IL-2] were significantly lower in the tumor-bearing group, whereas that of IL-4 were significantly higher [P<.05]. The number of CD4+T cells secreting interferon-gamma and the specific cytotoxicity of CD8+ cytotoxic T lymphocytes were significantly lower [P<.05]. The survival was significantly higher in the activated group compared with the other groups. Lymphocytes from tumor-bearing rats activated in vitro can effectively reverse the immunosuppressive effects of tumor-bearing hosts
Subject(s)
Animals , Lymphopenia/chemically induced , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cyclophosphamide , RatsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of maternal deprivation on the activity of hypothalamo-pituitary-adrenal (HPA) axis, acute stress response and the sex hormone receptors expression in hypothalamic paraventricular nucleus (PVN) in female rats.</p><p><b>METHODS</b>Maternal deprivation model was induced in female Sprague-Dawley (SD) rats. Foot shock was given at different stages of estrus cycle during the adulthood. Plasma estradiol, testosterone and adrenocorticotropin (ACTH) levels were determined by radioimmunoassay; and plasma corticosterone level was measured by enzyme linked immunosorbent assay. The expression of androgen receptor (AR) and estrogen receptor (ER-β) in the hypothalamic PVN was detected by immunohistochemistry.</p><p><b>RESULTS</b>Decreased plasma ACTH and corticosterone levels were found in the proestrus of female rats with maternal deprivation (P=0.012 and P=0.019, respectively). A significant down-regulation (P=0.008) of PVN-AR, but not PVN-ER-β expression was found in female rats with maternal deprivation.</p><p><b>CONCLUSION</b>Maternal deprivation may reduce the HPA axis activity in female SD rats, which is closely correlated with the fluctuation of the circulating sex hormones. The androgen in the hypothalamus seems to play a more important role than the estrogen in this procedure.</p>