Biomedical subjects

R Granstein

Publications and source records attributed to R Granstein.

4 recordsLinked to original sources

PubMed1998

Involvement of interleukin-3 in delayed-type hypersensitivity.

The in vivo functions of interleukin-3 (IL-3) were investigated by generating IL-3-deficient mice. Although hematopoiesis was unimpaired in homozygous mutant animals, contact hypersensitivity reactions were compromised. IL-3 was required for efficient priming of hapten-specific contact hypersensitivity responses, but was dispensable for T-cell-dependent sensitization to tumor cells. These findings reveal a critical role for IL-3 in some forms of delayed-type hypersensitivity.

Animals↗

PubMed1997

Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen beta-galactosidase (betagal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing betagal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.

Adenocarcinoma↗

PubMed1983

Molecular signals in antigen presentation. I. Effects of interleukin 1 and 2 on radiation-treated antigen-presenting cells in vivo and in vitro.

In order to clarify the nature of the defect in the process of antigen presentation caused by uv radiation, low-density spleen cells were used as a potent APC source in a hapten-specific cytolytic T-cell (Tc) system. It was demonstrated that IA+ weakly adherent low-density spleen cells, when directly coupled with azobenzene arsonate (ABA), led to the activation ABA-specific Tc. When these APC were exposed to uv radiation (12 J/m2/sec) for 30 sec, their ability to lead to Tc activation was markedly inhibited. The defect imposed by uv radiation could be specifically bypassed by the addition of small amounts of homogeneous IL-1 or IL-2. This led to the specific activation of ABA-reactive H-2-restricted Tc. The purified IL-1 was also found to bypass the systemic defect imposed in vivo by external uv radiation of mice. This may indicate a potential therapeutic role for IL-1.

Animals↗

PubMed1977

Transmembrane bone morphogenesis across multiple-walled diffusion chambers. New evidence for a diffusible bone morphogenetic property.

Bone generation and regeneration are associated with a bone morphogen that recruits mesenchymal cells for differentiation into bone. Experiments with particulate bone matrix gelatin implanted in multiple-walled diffusion chambers suggest that bone morphogen is a rapidly diffusible molecule, and consists of a noncollagenous bone morphogenetic protein (BMP). When particulate bone matrix gelatin is implanted inside of diffusion chambers constructed of two to five membranes, ranging from 300 to 750 cu micronm in total thickness, large deposits of bone develop on the outside. The volumes of the deposits of new bone are inversely proportional to the thickness (or distance) of transmission of the BMP. Transmission for long distances through interstitial fluid can be accounted for by a low molecular mass hydrophobic BMP, disseminated according to the laws of diffusion.

Animals↗