Abstract

This is a proposal to study the maturation of T lymphocyte progenitors in the bone marrow and thymus of mice. An in vitro technique for growing these progenitors to produce colonies (the CFU-pre-T assay) will be used to investigate the nature of progenitors, their changes with age, and their dependence upon a humoral factor or thymic hormone. The hormone which causes the proliferation and maturation of CFU-pre-T will be purified and characterized. The site where the generation of diversity takes place in developing T cells -bone marrow or thymus - will be determined by in vitro and in vivo clonal abortion experiments, and the number of clones in a normal thymus measured using X-linked enzyme variants. The nature of the interaction between developing thymocytes and epithelial """"""""nurse"""""""" cells will be investigated, to see if this has a central role in the generation of major histocompatibility complex restriction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI011661-12
Application #
3124992
Study Section
Immunobiology Study Section (IMB)
Project Start
1977-05-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Squier, M K; Sehnert, A J; Sellins, K S et al. (1999) Calpain and calpastatin regulate neutrophil apoptosis. J Cell Physiol 178:311-9
Squier, M K; Cohen, J J (1997) Calpain, an upstream regulator of thymocyte apoptosis. J Immunol 158:3690-7
Squier, M K; Miller, A C; Malkinson, A M et al. (1994) Calpain activation in apoptosis. J Cell Physiol 159:229-37
Sellins, K S; Cohen, J J (1991) Cytotoxic T lymphocytes induce different types of DNA damage in target cells of different origins. J Immunol 147:795-803
Owens, G P; Hahn, W E; Cohen, J J (1991) Identification of mRNAs associated with programmed cell death in immature thymocytes. Mol Cell Biol 11:4177-88
Sellins, K S; Cohen, J J (1991) Hyperthermia induces apoptosis in thymocytes. Radiat Res 126:88-95
Cohen, J J (1991) Programmed cell death in the immune system. Adv Immunol 50:55-85
McCall, C A; Cohen, J J (1991) Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease. J Invest Dermatol 97:111-4
Duke, R C (1989) Self recognition by T cells. I. Bystander killing of target cells bearing syngeneic MHC antigens. J Exp Med 170:59-71
Duke, R C; Persechini, P M; Chang, S et al. (1989) Purified perforin induces target cell lysis but not DNA fragmentation. J Exp Med 170:1451-6

Showing the most recent 10 out of 18 publications