Abstract

Differentiation of arrays of cells in the intact organism is accomplished by sequential display of specific molecules capable of transmitting information about their surroundings through intercellular intermediates to effect a change in the cell's genetic program. To approach the role of intercellular contact in determining differentiation, we propose to develop an in vitro system capable of mimicking cell-cell interactions, specifically between prothymocytes and thymic stroma cells. In this system, intimate cellular contact between the thymic stroma and the prothymocyte probably plays a major role in the initiation of differentiation of the prothymocyte into the major T-cell lineages. To test this hypothesis we propose to derive in vitro functional correlates of each cell type and to this end we will: A. Characterize the morphologically distinct stromal cell types we have clonally derived in vitro from the hyperplastic thymus of an SV40 transgenic mouse and determine the interactions that lead to proliferation and differentiation of the prothymocyte. B. Derive in vitro stable populations of replicating prothymocytes and determine if they are capable of differentiation by means of interaction with the thymic stromal cell lines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA018470-12A2
Application #
3164948
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-12-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Cerasoli, D M; McGrath, J; Carding, S R et al. (1995) Low avidity recognition of a class II-restricted neo-self peptide by virus-specific T cells. Int Immunol 7:935-45
Ye, X; Kralli, A; Ge, R et al. (1994) Down-regulation of MHC class I antigen in insulinoma cells controlled by the R1 element of the H-2 enhancer. Oncogene 9:1195-204
Ye, X; McCarrick, J; Jewett, L et al. (1994) Timely immunization subverts the development of peripheral nonresponsiveness and suppresses tumor development in simian virus 40 tumor antigen-transgenic mice. Proc Natl Acad Sci U S A 91:3916-20
Faas, S J; Rothstein, J L; Kreider, B L et al. (1993) Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. Eur J Immunol 23:1201-14
Simon, D; Knowles, B B (1993) Newly acquired peri-telomeric heterochromatin in a transgenic mouse lineage. Cytogenet Cell Genet 62:211-3
McCarrick 3rd, J W; Parnes, J R; Seong, R H et al. (1993) Positive-negative selection gene targeting with the diphtheria toxin A-chain gene in mouse embryonic stem cells. Transgenic Res 2:183-90
Rothstein, J L; Johnson, D; DeLoia, J A et al. (1992) Gene expression during preimplantation mouse development. Genes Dev 6:1190-201
Knowles, B B; Faas, S; Juretic, A et al. (1991) SV40 T antigen transgenic mice: cytotoxic T lymphocytes as a selective force in tumor progression. Basic Life Sci 57:111-24;discussion 125
Knowles, B B; McCarrick, J; Fox, N et al. (1990) Osteosarcomas in transgenic mice expressing an alpha-amylase-SV40 T-antigen hybrid gene. Am J Pathol 137:259-62
Fox, N; Crooke, R; Hwang, L H et al. (1989) Metastatic hibernomas in transgenic mice expressing an alpha-amylase-SV40 T antigen hybrid gene. Science 244:460-3

Showing the most recent 10 out of 21 publications