: Signaling Lymphocyte Activation Molecule (SLAM or CD 150) is a self-ligand receptor at the interface between T cells and professional antigen presenting cells (APCs). The notion that SLAM functions in T cells and APCs is supported by the following observations: --SLAM-deficient mice have abnormal responses to Leishmania major and airway hyper-responsiveness. Antibodies to SLAM block development of experimental colitis in mice. --Monoclonal antibodies directed at SLAM act as co-stimulators of T cell receptor driven DNA synthesis and cytokine gene activation in a CD28-independent manner. --The cytoplasmic tail of SLAM binds SAP (SH2D1A) in T cells and EAT-2 in APCs. These single free SH2-domain proteins can act either as natural inhibitors or as adapters. When the SAP gene is altered or deleted, a primary immunodeficiency, X-linked Lymphoproliferative (XLP) disease, develops. --SLAM is the primary receptor for Measles Virus, which causes a severe immune-suppressionThe experiments proposed in this application are designed to understand the contributions of SLAM to the function of T helper cells and APCs. The fundamental strategy is to examine the in vivo role of SLAM on T cells and macrophages in the pathogenesis of experimental colitis, airway hyper-responsiveness and infections with L. major. Furthermore, the role of SLAM in specific cytokine gene induction will be dissected at the cellular and biochemical level.
The specific aims are:
Aim# 1 Test the hypothesis that both macrophage and T helper cell functions are impaired in SLAM-deficient mice.
Aim#2 Test the hypothesis that SLAM signal transduction regulates the IL-4 and IFNgamma genes in T cells and the IL-12 and TNFalpha genes in macrophages.
Aim#3 Determine the function of the SLAM associated signal transduction protein ensemble in T cells and macrophages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015066-28
Application #
7094208
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Mallia, Conrad M
Project Start
1978-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
28
Fiscal Year
2006
Total Cost
$415,013
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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