The broad, long term objective of this application is to gain insight into the physiological role of gammadelta TCR+ T cell subsets. The studies propose include the following specific aims: 1. To characterize further the murine repertoire of gammadelta TCRs expressed during T cell development in the thymus. We will extend a collection of gammadelta+ thymocyte hybridomas using a novel T cell fusion line which is permissive for the surface expression of gammadelta: The gammadelta receptors will be analyzed, using PCR technology, cDNA cloning and sequencing, and two-dimensional gel electrophoresis of receptor proteins. 2. To test the concept that the entire gammadelta+ cell population, or large parts of it, consists of specialized local subsets, each of which bears one or a group of characteristic receptor molecules. We will purify gammadelta+ cells from different organs, including different lymphoid organs and lungs. We will analyze gamma and delta V gene expression in these cells. This study should provide us with some insight into the general organization of the gammadelta+ T cell population. 3. To study the reactivity of gammadelta+ T cells with alloantigens and self-MHC class I determinants. To detyermine frequencies of alloreactive gammadelta+ cells, we will test alloantigens as stimulators with a large panel of unselected gammadelta+ and alphabeta + hybridomas. To evaluate the possible role of MHC class I molecules, we will study the development of normal gammadelta cells in mice chronically injected with anti MHC class I antibodies. 4. To generate a alphabeta-gammadelta+ mouse model. We will use a new pan-specific anti-alphabeta antibody. Newborn animals will be chronically injected with this antibody to selectively suppress the development of alphabeta+ T cells. These mice will be studied as potential models for gammadelta cell funciton in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027903-02
Application #
3142200
Study Section
Immunobiology Study Section (IMB)
Project Start
1989-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206
Mukasa, A; Lahn, M; Fleming, S et al. (2002) Extensive and preferential Fas/Fas ligand-dependent death of gammadelta T cells following infection with Listeria monocytogenes. Scand J Immunol 56:233-47
Mukasa, A; Born, W K; O'Brien, R L (1999) Inflammation alone evokes the response of a TCR-invariant mouse gamma delta T cell subset. J Immunol 162:4910-3
Lahn, M; Kalataradi, H; Mittelstadt, P et al. (1998) Early preferential stimulation of gamma delta T cells by TNF-alpha. J Immunol 160:5221-30
Kelly, K A; O'Brien, R; Born, W (1997) Reconstitution of SCID mice with haemopoietic precursors: a detailed analysis of gamma delta T-cell reconstitution. Immunology 91:65-72
Roark, C E; Vollmer, M K; Campbell, P A et al. (1996) Response of a gamma delta+ T cell receptor invariant subset during bacterial infection. J Immunol 156:2214-20
Fu, Y X; Roark, C E; Kelly, K et al. (1994) Immune protection and control of inflammatory tissue necrosis by gamma delta T cells. J Immunol 153:3101-15
Roark, C E; Vollmer, M K; Cranfill, R L et al. (1993) Liver gamma delta T cells. TCR junctions reveal differences in heat shock protein-60-reactive cells in liver and spleen. J Immunol 150:4867-75
Born, W K; Harshan, K; Modlin, R L et al. (1991) The role of gamma delta T lymphocytes in infection. Curr Opin Immunol 3:455-9
Born, W K; O'Brien, R L; Modlin, R L (1991) Antigen specificity of gamma delta T lymphocytes. FASEB J 5:2699-705
Carbone, A; Harbeck, R; Dallas, A et al. (1991) Alpha beta T-lymphocyte depleted mice, a model for gamma delta T-lymphocyte functional studies. Immunol Rev 120:35-50

Showing the most recent 10 out of 11 publications