Much remains to be learned about the events responsible for the survival, expansion and differentiation of CD25plusCD4minusCD8minusthymocytes. A signal delivered by the pre-TCR is known to be sufficient, but not necessary, to reach the CD25minus CD4plus CD8plus stage in vivo. Recent observations suggest that CD81 expressed by thymic epithelial cells also plays a pivotal role in this process. It has been clearly shown that maturation of murine CD25plusCD4minusCD8minus cells to CD25minusCD4plusCD8plus cells can be induced in reaggregation culture by a CD81plus fetal thymic epithelial cell line as well as by other cell types transfected with a murine CD81 cDNA. These findings established that CD81 can transmit a developmental signal to CD4minusCD8minus cells possibly through a putative receptor. A combination of molecular and biochemical approaches will be employed for the identification of potential CD81 receptors expressed by CD4minusCD8minus thymocytes. The developmental relationship between pre-TCR and CD81 mediated signals will be investigated by evaluating the status of TCR-beta gene rearrangement in thymocytes recovered from anti-CD81 antibody treated fetal thymic organ cultures. These experiments should help provide a model to explain the demonstrated requirement of pre-TCR and CD81-mediated signals in early T cell development. Finally, the function of CD81 in early T cell development will be analyzed in vivo following antibody treatment and by using CD81 deficient mutant mice generated using the Cre-loxP system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI040616-04
Application #
6170083
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Ridge, John P
Project Start
1997-07-01
Project End
2001-03-31
Budget Start
2000-07-01
Budget End
2001-03-31
Support Year
4
Fiscal Year
2000
Total Cost
$91,875
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Witherden, D A; Boismenu, R; Havran, W L (2000) CD81 and CD28 costimulate T cells through distinct pathways. J Immunol 165:1902-9
Boismenu, R; Havran, W L (1998) Gammadelta T cells in host defense and epithelial cell biology. Clin Immunol Immunopathol 86:121-33