Abstract

This project aims to improve our understanding of what regulates T cell development in the thymus. Hence, it will have ramifications for our understanding and possible treatment of immuno-pathology in humans and in animals of agricultural importance. In particular, the thymus gives rise to two types of T cell: Alphabeta T cell receptor-bearing, and gammadelta T cell receptor- bearing. Molecular analyses of defined thymic progenitors will be used to ascertain when progenitor cells lose the potential to make both cell types, i.e. become committed to making one type or the other. These studies will be focused on testing a new working model for thymocyte development that we have been able to create based on our recent progress using normal and mutant mice that we have developed. Moreover, we shall continue to develop novel mouse mutants that are proving powerful in providing mechanistic insight into T cell development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM037759-06A1
Application #
3293435
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1987-07-01
Project End
1996-08-31
Budget Start
1993-09-20
Budget End
1994-08-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Douglas, N C; Jacobs, H; Bothwell, A L et al. (2001) Defining the specific physiological requirements for c-Myc in T cell development. Nat Immunol 2:307-15
Gibbons, D; Douglas, N C; Barber, D F et al. (2001) The biological activity of natural and mutant pTalpha alleles. J Exp Med 194:695-703
Barber, D F; Passoni, L; Wen, L et al. (1998) The expression in vivo of a second isoform of pT alpha: implications for the mechanism of pT alpha action. J Immunol 161:11-6
Mallick-Wood, C A; Lewis, J M; Richie, L I et al. (1998) Conservation of T cell receptor conformation in epidermal gammadelta cells with disrupted primary Vgamma gene usage. Science 279:1729-33
Sant'Angelo, D B; Waterbury, P G; Cohen, B E et al. (1997) The imprint of intrathymic self-peptides on the mature T cell receptor repertoire. Immunity 7:517-24
Passoni, L; Hoffman, E S; Kim, S et al. (1997) Intrathymic delta selection events in gammadelta cell development. Immunity 7:83-95
Mallick-Wood, C A; Pao, W; Cheng, A M et al. (1996) Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase. Proc Natl Acad Sci U S A 93:9704-9
O'Shea, C C; Crompton, T; Rosewell, I R et al. (1996) Raf regulates positive selection. Eur J Immunol 26:2350-5
Kiyokawa, H; Kineman, R D; Manova-Todorova, K O et al. (1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85:721-32
Burtrum, D B; Kim, S; Dudley, E C et al. (1996) TCR gene recombination and alpha beta-gamma delta lineage divergence: productive TCR-beta rearrangement is neither exclusive nor preclusive of gamma delta cell development. J Immunol 157:4293-6

Showing the most recent 10 out of 32 publications