| First Author | Zou L | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 4 | Pages | 986-94 |
| PubMed ID | 18383041 | Mgi Jnum | J:133782 |
| Mgi Id | MGI:3784137 | Doi | 10.1002/eji.200737881 |
| Citation | Zou L, et al. (2008) Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP-deficient BDC2.5-C57BL/6 mice. Eur J Immunol 38(4):986-94 |
| abstractText | 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. |
