Runx3 Regulates CD8 T Cell Local Expansion and CD43 Glycosylation in Mice by H1N1 Influenza A Virus Infection

We have recently reported that transcription factor Runx3 is required for pulmonary generation of CD8 cytotoxic T lymphocytes (CTLs) that play a crucial role in the clearance of influenza A virus (IAV). To understand the underlying mechanisms, we determined the effects of knockout (KO) on CD8 T cell local expansion and phenotypes using an inducible general KO mouse model. We found that in contrast to the lungs, general KO promoted enlargement of lung-draining mediastinal lymph node (mLN) and enhanced CD8 and CD4 T cell expansion during H1N1 IAV infection. We further found that deficiency greatly inhibited core 2 O-glycosylation of selectin ligand CD43 on activated CD8 T cells but minimally affected the cell surface expression of CD43, activation markers (CD44 and CD69) and cell adhesion molecules (CD11a and CD54). KO had a minor effect on lung effector CD8 T cell death by IAV infection. Our findings indicate that Runx3 differently regulates CD8 T cell expansion in mLNs and lungs by H1N1 IAV infection. Runx3 is required for CD43 core 2 O-glycosylation on activated CD8 T cells, and the involved Runx3 signal pathway may mediate CD8 T cell phenotype for pulmonary generation of CTLs.