Persistence and Function of Central and Effector Memory CD4+ T Cells following Infection with a Gastrointestinal Helminth

Abstract

Immunity in the gastrointestinal tract is important for resistance to many pathogens, but the memory T cells that mediate such immunity are poorly characterized. In this study, we show that following sterile cure of a primary infection with the gastrointestinal parasite Trichuris muris, memory CD4+ T cells persist in the draining mesenteric lymph node and protect mice against reinfection. The memory CD4+ T cells that developed were a heterogeneous population, consisting of both CD62Lhigh central memory T cells (TCM) and CD62Llow effector memory T cells (TEM) that were competent to produce the Th type 2 effector cytokine, IL-4. Unlike memory T cells that develop following exposure to several other pathogens, both CD4+ TCM and TEM populations persisted in the absence of chronic infection, and, critically, both populations were able to transfer protective immunity to naive recipients. CD62LhighCD4+ TCM were not apparent early after infection, but emerged following clearance of primary infection, suggesting that they may be derived from CD4+ TEM. Consistent with this theory, transfer of CD62LlowCD4+ TEM into naive recipients resulted in the development of a population of protective CD62LhighCD4+ TCM. Taken together, these studies show that distinct subsets of memory CD4+ T cells develop after infection with Trichuris, persist in the GALT, and mediate protective immunity to rechallenge.