Differential Expression of p95^vav in Primary Lymphoid Tissue of BB Rats Congenic for the Lymphopenia Gene

Abstract

Lyp controls lymphopenia and T-cell mediated autoimmune diabetes in the Bio Breeding (BB) rat possibly by interacting with T-cell maturation in the thymus. The protooncogene vav (p95) is involved in T-cell activation and in the intrathymic selection of developing T cells. We have previously reported increased production of IFN-γ of self reactive thymocytes in the thymus medulla of Lyp/Lyp BB rats. Lymphopenia and diabetes may therefore be linked to an increase in thymocyte activation leading to a bias in thymocyte development. The purpose of this study was therefore to investigate whether the expression of p95^vav in primary lymphoid tissues from congenic Lyp/Lyp, Lyp/+ and +/+ BB rats was correlated to the Lyp genotype using in situ hybridization and reverse transcription (RT)-PCR. It was found that the expression of vav mRNA in the thymus was increased in Lyp/Lyp compared to Lyp/+ and +/+ rats (p < 0.05). Western blot analysis revealed that the amount of p95^vav protein in Lyp/Lyp thymus was also increased. The results show that vav expression correlates with the lymphopenia phenotype and diabetes development in congenic Lyp/Lyp BB rats. An increase in the availability of p95^vav during the development and activation of thymocytes in Lyp/Lyp BB rats may therefore contribute to the generation of islet autoreactivity, lymphopenia or both.

Key Words:

• Type 1 diabetes
• Cytokines
• Autoreactivity
• Signal transduction