X-linked lymphoproliferative disease (XLP) is a human disease characterized by hypogammaglobulinemia that results from mutations in a gene encoding SLAM-associated protein (SAP), which facilitates signaling in T cells. Although CD4 T cell responses are intact in SAP-deficient (SAP-) mice, SAP is required in CD4 T cells for normal plasma cell responses against viral infection, suggesting that a critical B cell helper function of CD4 T cells is missing when CD4 T cells lack SAP. However, when or in what form this helper function is delivered is unknown. We hypothesize that CD4 T cells can migrate into B cell follicles but cannot deliver SAP-dependent survival signals to B cells early in the immune response such that the B cells die by apoptosis. To test this hypothesis, we will determine when during an immune response SAP is required by reconstituting SAP- mice with wild type CD4 T cells at different times (aim I). We will then compare migration of SAP and wild type CD4 T cells during the immune response (aim II). Finally, we will identify the fate of B cells and plasma cells in SAP- mice by determining whether there is altered apoptosis, proliferation, or differentiation of these cells (aim III), which will suggest potential CD4 T cell defects to further analyze. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI066684-02
Application #
7090585
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$52,048
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
020658969
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983
Kamperschroer, Cris; Roberts, Deborah M; Zhang, Yongqing et al. (2008) SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation. J Immunol 181:3994-4003
Kamperschroer, Cris; Dibble, John P; Meents, Dana L et al. (2006) SAP is required for Th cell function and for immunity to influenza. J Immunol 177:5317-27