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.

The Central Memory CD4+ T Cell Population Generated duringLeishmania majorInfection Requires IL-12 to Produce IFN-γ

“…Consistent with this, we found that Trichuris muris infection induces a population of IL-4-competent memory CD4 ϩ T cells that express CD62L (37). In contrast, we show in this study that Tcm cells generated by L. major infection can become either IFN-␥-or IL-4-producing T cells, suggesting that these cells were not derived from effector T cells.…”

Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors

“…S2b). Consistent with results from work studying CD4 T cells in 4get mice after treatment of a parasitic infection (32,33), Ϸ10-25% of the memory cells derived from GFP ϩ cells were GFP lo in some samples at the time of recovery, whereas the rest were GFP Ϫ (Fig. S2c).…”

Accumulation of Effector CD4 T Cells during Type 2 Immune Responses Is Negatively Regulated by Stat6

“…Although extensive studies have been performed to characterize memory CD8 T cells and Th1-polarized memory CD4 T cells (40), relatively little is currently known about the phenotype, survival, and function of memory Th2 cells. Recent publications indicated that long-term memory Th2 cells display a central memory phenotype (CD62L high CD44 high ) and provide protection against helminth and protozoan parasites (41,42). Memory Th2 cells have been shown to accumulate at the host: parasite interface during secondary infections with the helminth parasite Heligmosomoides polygyrus and might enhance parasite clearance by inducing the differentiation of alternatively activated macrophages (43,44).…”