Recently our laboratory has developed a new model of murine lupus based on the injection of BALB/c anti-CD1 transgenic T cells into BALB/c nude mice. Host develop anti-DNA antibodies, proteinuria, glomerulonephritis, ascites and anemia. Transgenic CD4+ and CD8+ Tcells induce the disease, and transgenic CD4- CD8- T cells recognize the CD1 molecule on the surface of subsets of B cells, and polyclonally activate the latter cells to secrete lgG and pathogenic autoantibodies. We theorize that the anti-CD1-inducing T cells also help B cells to make antibody responses to polysaccaride antigens such as SSIII and alpha 1,3 dextran via interaction with the CD1 molecule (itself or as antigen presenting molecule for sugar residues). The suppressing transgenic T cells are theorized to inhibit their responses. In order to test the hypothesis, inducing and suppressing purified transgenic T cells will be added to B cell sources in vitro to assay for the secretion oflgG and anti-DNA antibodies in vitro. In similar studies, the ability of these anti-CD1 T cells to regulate the in vitro and in vivo polysaccharide antibody responses will be examined. ELISA assays for lg subclasses and anti-DNA antibodies will be used. The cytokine secretion pattern of the inducing and suppressing cells will be compared to help used the different functions of anti-CD1 T cells. The possible role of CD1 molecules as an understand the different function of anti-CD1 T cells. The possible role of CD1 molecules as an autoantigen in heredity mouse models of lipus (NZB/NZW) will be explored also by attempting to block spontaneous autoantibody secretion in vitro and in vivo with anti-CD1 antibodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040093-03
Application #
2887243
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Collier, Elaine S
Project Start
1997-05-01
Project End
2002-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Takahashi, Tsuyoshi; Strober, Samuel (2008) Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice interact to generate IgM and IgG autoantibodies. Eur J Immunol 38:156-65
Zeng, D; Lewis, D; Dejbakhsh-Jones, S et al. (1999) Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J Exp Med 189:1073-81