Biomedical subjects

D Pardoll

Publications and source records attributed to D Pardoll.

6 recordsLinked to original sources

PubMed1992

Molecular analysis of a pro-T cell clone transformed by Abelson-murine leukemia virus, displaying progressive gamma delta T cell receptor gene rearrangement and surface expression.

We present a molecular analysis of T cell differentiation in a set of clones derived from in vitro Abelson murine leukemia virus (A-MuLV) infection of fetal liver cells. The parental clone had partial rearrangement of the beta and gamma loci and spontaneously displayed progressive rearrangement of V gamma genes during in vitro culture. Further differentiation of these clones leading to delta gene rearrangement and CD4 expression, then CD8, CD3 and T cell receptor gamma delta chain surface expression was obtained after intrathymic transfer followed by in vitro co-culture with thymic tissue. These A-MuLV clones, therefore, appear to represent a powerful model system for studying the early molecular events of T cell development at the clonal level.

Abelson murine leukemia virus↗

PubMed1992

Thymic selection.

The ability of T cells to recognize foreign antigens, distinguish them from self antigens, and regulate immune responses depends largely on which of the vast array of different T-cell receptors they display on their surface, the so called T-cell repertoire. Two selection processes, positive and negative selection, operate on developing T cells and allow only a subset of all possible T cells to differentiate. New developments in transgenic mouse technology and the study of T-cell signalling are unravelling these fascinating processes.

Animals↗

PubMed1992

New strategies for active immunotherapy with genetically engineered tumor cells.

While previous tumor vaccine strategies have shown intriguing results, clearcut efficacy has been difficult to establish in human trials. Recently, newer approaches have been developed in animal systems that modify tumor cells genetically so that they express new antigens or secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigen or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity.

Genes, MHC Class II↗

PubMed1992

Immunotherapy with cytokine gene-transduced tumor cells: the next wave in gene therapy for cancer.

Recently, new tumor vaccine approaches were developed in animal systems that modify tumor cells genetically to secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigens or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. The development of high efficiency gene transfer technologies such as defective retroviral vectors allows for the translation of these preclinical studies to clinical trials. However, before large investments are made in this area of gene therapy, it will be important to demonstrate that the actual gene transfer component of the strategy significantly enhances antitumor immune responses relative to alternative nongenetic approaches.

Cytokines↗

PubMed1991

A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations.

To elucidate the molecular biology of the hematopoietic stem cell, we have begun to isolate genes from murine cell populations enriched in stem cell activity. One such cDNA encodes a novel receptor tyrosine kinase, designated fetal liver kinase-2 or flk-2, which is related to the W locus gene product c-kit. Expression analyses suggest an extremely restricted distribution of flk-2. It is expressed in populations enriched for stem cells and primitive uncommitted progenitors, and is absent in populations containing more mature cells. Therefore, this receptor may be a key signal transducing component in the totipotent hematopoietic stem cell and its immediate self-renewing progeny.

Amino Acid Sequence↗

PubMed1976

Evidence that mismatched bases in heteroduplex T4 bacteriophage are recognized in vivo.

T4 heteroduplex heterozygotes are lost selectively after prolonged incubation of phage-infected Escherichia coli cells under nonreplicating conditions. The loss of heterozygosity occurs for four out of six rII sites tested and is not dependent upon T4 v gene function. The results are interpreted to indicate the existence of a base-specific system for the recognition of mismatched bases in intracellular DNA.

Coliphages↗