The immune response combines extraordinary specificity of recognition with extremely complex control mechanisms that govern its effector mechanisms. Childhood primary immunodeficiency disorders can be viewed as experiments of nature in which a discrete genetic defect affects the expression and/or the structure/function of essential lymphocyte proteins and results in immune dysfunctions. A molecular or genetic definition of primary immunodeficiencies is essential for accurate diagnosis and therapy of the disorders and for better understanding of normal immune functions. In this program project, we propose to study a limited set of immunological diseases because of our success in analyzing both patient materials as well as genetic animal models. We will use recently acquired insights into the causes of the X-linked Lympho Proliferative disease (XLP), severe combined immunodeficiencies (SCID), Omenn syndrome and Common Variable Immunodeficiencies caused by T cell signaling defects in the XLP gene and in the critical adapter protein SLP-76. Our genetic animal models will become powerful tools for a systematic dissection of the biochemical processes involved in the pathogenesis of these diseases, but they will also shed light on basic mechanisms that govern ontogeny of the immune system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI035714-07
Application #
6170084
Study Section
Special Emphasis Panel (ZAI1-PSS-A (M1))
Program Officer
Wiesch, Denise
Project Start
1994-08-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
7
Fiscal Year
2000
Total Cost
$1,097,555
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Detre, Cynthia; Keszei, Marton; Romero, Xavier et al. (2010) SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions. Semin Immunopathol 32:157-71
Sintes, Jordi; Romero, Xavier; de Salort, Jose et al. (2010) Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-induced cytokine secretion by macrophages. J Leukoc Biol 88:687-97
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