Lymphopenia-induced CD4 T cell proliferation leads to bystander activation of CD8 T cells with increased gut-homing specificity (LYM6P.722)

Abstract

Abstract In the presence of high levels of certain cytokines, such as IL-2 and/or IL-15, and self-peptide-TCR interaction, CD8 T cells undergo strong proliferation, referred to as “bystander proliferation”. Up to now, bystander activated CD8 T cells have not been investigated on a role in normal condition. In order to define a role of bystander activated CD8 T cells, we co-transferred OT-I T cells with naïve polyclonal CD4 T cells into conventional immunodeficient Rag-/- mice to make CD4 T cells be activated in response to commensal microbiota and secrete large amount of IL-2. The bystander activated OT-I T cells which were driven by IL-2 from activated CD4 T cells underwent massive proliferation, acquired effector functions, up-regulated a4b7 and migrated into mostly gut. Moreover, we induced OT-I T cells to undergo bystander proliferation in normal conventional B6 hosts by co-injection of smarta CD4 T cells, a strong inducer of IL-2, after LCMV injection and by depletion of host T cells to increase consumption of IL-2 for donor OT-I T cells. Interestingly, bystander activated OT-I T cells driven by IL-2 from activated smarta CD4 T cells in normal conventional B6 hosts also up-regulated a4b7 and migrated into gut. Based on the finding, we will further investigate on the role of bystander activated CD8 T cells to protect against mucosal infection, such as Listeria monocytogenes-OVA (LM-OVA) and the factor for up-regulating a4b7 on bystander activated CD8 T cells.