Functional Analysis of Effector and Regulatory T Cells in a Parasitic Nematode Infection

Abstract
Parasitic nematodes typically modulate T-cell reactivity, primarily during the chronic phase of infection. We analyzed the role of CD4-positive (CD4+) T effector (Teff) cells and regulatory T (Treg) cells derived from mice chronically infected with the intestinal nematodeHeligmosomoides polygyrus. Different CD4+T-cell subsets were transferred into naïve recipients that were subsequently infected withH. polygyrus. Adoptive transfer of conventional Teffcells conferred protection and led to a significant decrease in the worm burdens ofH. polygyrus-infected recipients. Roughly 0.2% of the CD4+T cells wereH. polygyrusspecific based on expression of CD154, and cells producing interleukin 4 (IL-4) and IL-13 were highly enriched within the CD154+population. In contrast, adoptive transfer of Tregcells, characterized by the markers CD25 and CD103 and the transcription factor Foxp3, had no effect on the worm burdens of recipients. Further analysis showed that soon after infection, the number of Foxp3+Tregcells temporarily increased in the inflamed tissue while effector/memory-like CD103+Foxp+Tregcells systemically increased in the draining lymph nodes and spleen. In addition, Tregcells represented a potential source of IL-10 and reduced the expression of IL-4. Finally, under in vitro conditions, Tregcells from infected mice were more potent suppressors than cells derived from naïve mice. In conclusion, our data indicate that small numbers of Teffcells have the ability to promote host protective immune responses, even in the presence of Tregcells.