Both cortical thymocytes and """"""""mature"""""""" medullary thymocytes are derived from dividing lymphoblastoid precursors in the thymus. It is unknown whether the precursor cells are already committed to helper or cytotoxic lineages, and whether they themselves are immunocompetent. We will isolate these stem cells from the thymus and test them directly for functional reactivity. We will subfractionate them according to their expression of peanut agglutinin binding sistes, thymus leukemia antigen, and the lineage marker Lyt-2/3, and measure the stability of these phenotypic characteristicss in vitro. The functional reactivities of the different blast cell populations will then be compared, using limiting dilution cultures to determine the frequencies of responding cells. The assays will measure colony formation in response to alloantigens or polyclonal mitogens, and inducible secretion of the helper factor interleukin-2. We will also test whether the pre-killer thymic lymphoblasts exhibit as strong a preference for class I histocompatibility antigen targets as pre-killer cells that have emigrated from the thymus, and whether the early pre-helper cells already show a preference for class II targets. To dissect the development of immune competence, we will study the regulation of IL-2 receptor expression in stem cells, postmitotic thymocytes, and peripheral T cells: thus, we will test whether populations that mount weak proliferative responses are defective in their expression of this receptor. Finally, we will lay the groundwork for a molecular analysis of T-cell triggering throughout development by using DNA-mediated gene transfer and molecular cloning to isolate the gene for the mouse IL-2 receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019752-04
Application #
3129152
Study Section
Immunobiology Study Section (IMB)
Project Start
1982-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Yang-Snyder, J A; Rothenberg, E V (1998) Spontaneous expression of interleukin-2 in vivo in specific tissues of young mice. Dev Immunol 5:223-45
Scherer, L J; Diamond, R A; Rothenberg, E V (1994) Developmental regulation of cAMP signaling pathways in thymocyte development. Thymus 23:231-57
Rothenberg, E V (1994) Signaling mechanisms in thymocyte selection. Curr Opin Immunol 6:257-65
Rothenberg, E V; Diamond, R A (1994) Costimulation by interleukin-1 of multiple activation responses in a developmentally restricted subset of immature thymocytes. Eur J Immunol 24:24-33
Rothenberg, E V; Diamond, R A; Chen, D (1994) Programming for recognition and programming for response. Separate developmental subroutines in the murine thymus. Thymus 22:215-44
Rothenberg, E V; Chen, D; Diamond, R A (1993) Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point. J Immunol 151:3530-46
Chen, D; Rothenberg, E V (1993) Molecular basis for developmental changes in interleukin-2 gene inducibility. Mol Cell Biol 13:228-37
Yang-Snyder, J A; Rothenberg, E V (1993) Developmental and anatomical patterns of IL-2 gene expression in vivo in the murine thymus. Dev Immunol 3:85-102
Rothenberg, E V (1992) The development of functionally responsive T cells. Adv Immunol 51:85-214
Novak, T J; Yoshimura, F K; Rothenberg, E V (1992) In vitro transfection of fresh thymocytes and T cells shows subset-specific expression of viral promoters. Mol Cell Biol 12:1515-27

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