Liangxing Zou

E-mail: zoux0019@umn.edu

Thesis Advisor: Erik Peterson

Year entered: 2002

Degrees received:
B.S., Biochemistry, Nanchang University, Jianyxi, China 1998
M.S., Molecular Genetics, Institute of Genetics, Beijing, China, 2000

Honors and Awards:

• MICaB travel award 2004

Thesis research:
Adhesion and degranulation promoting adapter protein (ADAP), a positive regulator of T cell receptor (TCR) signaling, is required for thymocyte development and T cell homeostasis. To investigate the role of ADAP in a T cell-driven autoimmune response, we generated ADAP-deficient, BDC2.5 TCR transgenic, diabetes-prone (C57BL/6) mice (BDC/B6). We observed a striking enhancement of diabetes incidence in ADAP-deficient mice, both in animals homozygous for I-A(g7), and in mice carrying one I-A(b) allele (BDC/B6(g7/b)). Increased disease correlates with significantly reduced numbers of pathological CD4(+) T cells in the mice. Consistent with a state of functional lymphopenia in ADAP-deficient BDC/B6(g7/b) mice, T cells display increased homeostatic proliferation. Transfer of syngeneic lymphocytes or T cells both blocks ADAP-dependent diabetes and relieves exaggerated homeostatic T cell proliferation observed in ADAP-deficient mice. Marked attenuation in cellularity of the CD4(+) single-positive thymocyte compartment in ADAP-deficient BDC/B6(g7/b) animals suggests a mechanism for induction of the lymphopenia. We conclude that inefficient positive selection in ADAP deficiency results in lymphopenia that leads to enhanced autoimmune diabetes in the BDC/B6(g7/b) model. Our findings support the notion that ineffective thymic T cell output can be a powerful causative factor in lymphopenia-driven autoimmune diabetes.

Publications:

• Zou L, Mendez F, Martin-Orozco N, and Peterson EJ. 2008. “Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP deficient BDC2.5-Bl/6 mice”. Journal of Immunology Mar 26;38(4):986-994.

• Dluzniewska J, Zou L, Harmon IR, Ellingson MT, Peterson EJ. 2008. 1 “Immature hematopoietic cells display selective requirements for adhesion- and degranulation-promoting adaptor protein in development and homeostatsis”. European Journal of Immunology 37, 3208.