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Adjuvants modulate protective CD8+T cell responses generated by cancer vaccines. We have previously shown that immunostimulatory cytosine–phosphodiester–guanine (CpG) oligodeoxynucleotide (ODN) significantly augments tumor protection in mice given adenovirus cancer vaccines. Here, we examined the impact of chitosan, another candidate vaccine adjuvant, on protection conferred by adenovirus cancer vaccines. Unexpectedly, immunization of mice with adenovirus cancer vaccines in combination with chitosan provided little protection against tumor challenge. This directly correlated with the reduced detection of Ag-specific CD8+T cells, interferon-γ (IFN-γ) production, and cytotoxic T cell activity. We ruled out immunosuppressive regulatory T cells since the frequency did not change regardless of whether chitosan was delivered. In mammalian cell lines, chitosan did not interfere with adenovirus transgene expression. However, infection of primary murine bone marrow-derived dendritic cells with adenovirus complexed with chitosan significantly reduced viability, transgene expression, and upregulation of major histocompatability (MHC) class I and CD86. Our in vitroobservations indicate that chitosan dramatically inhibits adenovirus-mediated transgene expression and antigen presenting cell activation, which could prevent CD8+T cell activation from occurring in vivo. These surprising data demonstrate for the first time that chitosan vaccine formulations can negatively impact the induction of CD8+T cell responses via its effect on dendritic cells, which is clinically important since consideration of chitosan as an adjuvant for vaccine formulations is growing.

The development of a tissue culture line of human prostatic adenocarcinoma is described. The culture (HPC-36), derived from tumor tissue explants, is a pure epithelial culture with characteristics of neoplastic cells, including a large nuclear size relative to the amount of cytoplasm, multiple nucleoli within the nucleus, many mitotic figures, the formation of multinucleated giant cells and the loss of contact inhibition. The cells also stained positively for acid phosphatase and have been grown in monolayer and suspension cultures. The HPC-36 cells presently are being studied to determine whether they are true descendants of the cancer cells.

Many investigators have reported effects of the pituitary hormone, prolactin, on the physiology and biochemistry of the rat prostate gland, particularly the lateral or dorsolateral lobe. The Dunning R3327H is a transplantable rat prostatic adenocarcinoma derived from a spontaneous tumor of the Copenhagen rat dorsolateral prostate. This study describes and compares morphological and physiological effects of prolactin on rat dorsolateral prostate and two sublines of the Dunning tumor. Ectopic pituitary grafts were used to induce chronic hyperprolactinemia in castrated rats receiving androgen supplement to provide a relatively controlled hormonal environment in which the effects of prolactin were maximally and consistently observed. Gravimetric and biochemical analyses, as well as ultrastructural study, provided evidence of prolactin’s stimulatory effect on dorsolateral prostate growth and secretory activity. Hyperprolactinemia stimulated the growth of the well-differentiated, androgen-dependent R3327/3219 tumor subline with an increase in weight, volume and the total content of DNA, protein and zinc. There were no changes in tumor morphology. In contrast, the anaplastic androgen-independent R3327/150 tumor subline did not respond to graft-induced hyperprolactinemia. This differential response of the two R3327 tumor sublines attests to the complexity of prolactin’s effects on prostatic tissue and to the extent of the deterioration of endocrine control that often accompanies tumor progression. Prolactin binding in the R3327 sublines was studied using immunohistochemical staining and radioligand assay, but produced complex results which raise questions about the discrepancy between hormone binding and biological action of prolactin in prostatic tissues.

ABSTRACTThe pathogenic Neisseriaspecies induce cytoskeletal reorganization in immortalized cell lines. In Chang conjunctival epithelium and T84 intestinal epithelium, focal cytoskeletal rearrangements in which bacteria contacted the epithelial surface were observed. We show that actin footprints are induced in gonococcus-challenged primary urethral epithelium. Moreover, the microbes induced microvillus extension from the epithelial cell surface. Our results indicate that formation of actin footprints is not an artifact of commonly used immortalized cell lines.

Splenectomy or thymectomy of adult Lewis rats following sensitization with tubercle bacilli did not affect their ability to develop delayed skin lesions upon skin testing with PPD. The presence of the thymus also had no significant effect on reactivity of the recipients in passive transfer experiments. The passive transfer of tuberculin hypersensitivity with sensitized lymph node cells to thymectomized, irradiated recipients depended on the simultaneous or prior injection of normal bone marrow cells. When lymph node cell transfer was performed shortly after irradiation and injection of marrow, high doses of marrow cells (3.5–4.0 x 108 were required to permit eliciting reactions of reasonable intensity. If, however, periods of 7–10 days elapsed between the injection of bone marrow and sensitized lymph node cells, lower doses of marrow were sufficient for comparable reactions. Normal thymus, spleen, lymph node, or peritoneal exudate cells, even at high doses could not be substituted for the bone marrow in producing good tuberculin reactions.

The role of bone marrow-derived cells in the rejection of skin allografts in rats was investigated. Lewis rats, rendered tolerant of BN antigens and bearing healthy grafts, were thymectomized, irradiated with 900 rad, and injected with varying doses of either normal isologous bone marrow, normal lymph node cells, and/or lymph node cells presensitized to BN antigens. In some experiments rats were also adoptively sensitized to tuberculin. Results showed that, although necessary for the elicitation of tuberculin skin reactions, bone marrow cells are not needed for the rejection of previously tolerated skin allografts. Rats receiving lymph node cells alone rejected their grafts in about 6–7 days. In addition, rats injected with bone marrow alone also rejected their grafts, although significantly later than did lymph node cell recipients, indicating that rat marrow contains a population of cells capable of reacting to transplantation antigens. These cells were found capable of reacting to major transplantation antigens but not minor as they were ineffective in causing the rejection of Ag-B compatible Fischer skin grafts. From experiments utilizing bone marrow from neonatally thymectomized donors and cells treated with an antiserum to rat T cells, these competent cells in the marrow were shown to be thymus derived.