CD8aa-specific CD8ab Effector Memory T Cell Differentiation in the Gut (42.6)

Abstract

Abstract CD8 effector memory T cells at the intestinal mucosa are important for rapid containment of the invading pathogens. CD8aa, a homodimer of CD8a, has been found on gut intraepithelial lymphocytes (IELs). It is also transiently expressed on some peripheral CD8ab primary effector T cells that differentiate to memory T cells. In vitro stimulated sorted CD8aa+ and CD8aa− OT-I cells migrate with equal capacity to the gut and spleen of recipient mice. One month later, oral re-challenge with Listeria Monocytogenes-OVA (LM-OVA) leads to an immediate secondary expansion of CD8aa+, but not CD8aa−, donor cells among the IELs, which suggests that only CD8aa+ precursors can differentiate into mucosal memory T cells and respond immediately to an oral pathogen challenge. Later, both CD8aa+ and CD8aa− donor cell-derived secondary responses are detected in spleen and gut. However, 45 days after the secondary response, only CD8aa+donor cells generate memory IELs. It indicates that CD8aa+ primary effector cells are programmed during the initial priming to survive and to become mucosal effector memory T cells. CD8aa expression is transient on primary effector cells and regained after relocation into the gut. The specific role of CD8aa in the survival and differentiation of intestinal CD8 effector memory T cells was investigated.