Phenotypic and Functional Analysis of Regulatory T Cells during Heligmosomoides polygyrus infection

Abstract

Helminths are known to stimulate regulatory T cells, which have been shown to downregulate inflammatory as well as allergic conditions such as Crohn’s Disease, Ulcerative Colitis and allergic asthma respectively. However, the differences in the Tregs generated during helminth infection compared to steady state natural T regs have yet to be fully elucidated. Classically, in mice, Tregs are defined as CD4+CD25+ T cells. We have demonstrated that, unlike in BALB/c mice, in C57BL/6 animals, infection with the gastrointestinal nematode Heligmosomoides polygyrus does not result in increased CD4+CD25+-mediated suppressive activity. Using two different infection protocols, we characterized the CD4+CD25+ Treg-mediated response to acute and chronic infection from two different gut lymphoid organs, the Peyers patches and mesenteric lymph nodes. Unexpectedly, we found Tregs isolated from infected animals to be equally or less suppressive compared to those from naïve controls. However, we found no difference in the expression of Helios or CTLA-4, markers that play a role in control of the regulatory T cell phenotype and suppress T cell responses, respectively. These data indicate that manipulation of Tregs by helminths are more complex than previously thought and require more investigation into their suppressive profiles.