Transgenic mice expressing functional CD8αβ without an active CD8αα implies the contribution of CD8αα in the biological function of CD8αα+TCRαβ+ iIELs (P1466)

Abstract

Abstract To understand the functional significance of CD8αα complexes in vivo, we generated Tg mice carrying a variant CD8αβ (CD8αm3β) capable of forming inactive CD8αα/pMHCI complexes. These mice show a sub-optimal thymic differentiation with reduced populations of CD8 single-positive thymocytes. Tg CD8 T cells exhibit a compromised developmental capacity when competing with CD8 T cells from B6 mice in the adoptive bone marrow transferred host. However, once emigrated to the peripheral lymphoid organs, these CD8 T cells exhibit normal effector function against viral infection. Furthermore, TCRαβ+ T cell populations expressing CD8αβ+ or CD8αα+ reduced to about 50% in our Tg mice compared to normal B6 mice, and none of these CD8αα+TCRαβ+ T cells were stained by TL tetramer. Furthermore, this mice shows reduced infmmatory responses in DSS-induced colitis model. The findings obtained from our Tg animal models are going to be important to dissect the distinct functions of CD8αα molecule.