Highly functional Th2 effector cells coexist with IFN-g competent Th2/1 hybrid cells in the liver of nematode infected mice

Abstract text

Introduction

The small intestinal nematode Heligmosoides polygyrus establishes chronic infections in most mouse lines despite the induction of strong Th2 responses. We previously identified IFN-g competent Th2/1 hybrid cells as confounders of effective type 2 immunity in H. polygyrus infected mice and showed recently that age- and genotype-dependent differences in resistance to the infection correlate with the proportion of Th2/1 hybrid cells in nematode-induced CD4+GATA-3+ T cells.

Objectives

Th2/1 hybrid cells are relatively rare in the gut draining lymph nodes but may account for about half of the GATA-3+ effector cells in spleen and blood. We therefore investigated which other sites might serve as sources for nematode induced Th2/1 cells.

Materials and methods

We used the Heligmosoides polygyrus model for studying immune responses to helminth in C57BL/6 mice. A multi-color flowcytometric technique, as well as other enzyme-linked assay was also used to investigate the expression of type 1 and 2 immune markers on T cells after ex vivo cultures.

Results

We observed large numbers of GATA-3+ cells accumulating in the liver early during infection. These were enriched in Th2/1 cells, maintained during memory formation, and rapidly reactivated upon challenge infection in drug cured mice. Fitting the strong hepatic accumulation of CXCR3+ Th2/1 cells, myeloid cells isolated from the liver of infected mice stood out in the spontaneous production of the CXCR3-ligand CXCL9.

Conclusion

Together, these data suggest that IFN-g released early during worm infection results in the induction and systemic accumulation of IFN-g-competent type 2 effector cells. Whether spleen and liver limit excessive hybrid responses via apoptosis or benefit from Th2/1 accumulation in the surveillance of microbial translocation in enteric nematode infection is under current investigation.