Differential generation of parasite-specific Th2 and T follicular helper cells distinguishes resistant and susceptible mouse strains.

BACKGROUND

Both T helper 2 (Th2) and B cell responses are crucial for controlling gastrointestinal (GI) nematode infections. However, adaptive immune determinants of host susceptibility to GI nematode infection are still not fully understood.

METHODS

Adaptive immune responses against the small intestinal nematode Heligmosomoides polygyrus bakeri were compared between susceptible C57BL/6 and resistant BALB/c mice. Parasite-specific Th2 responses were quantified via combined detection of CD40-L and type 2 cytokine expression in CD4+GATA-3high cells stimulated with parasite products. Follicular T helper cell (TFH) and germinal center B cell responses were determined in parallel. Potential effects of the different Treg activity evident early during infection were tested by IL-2-induced Treg expansion in C57BL/6 and transient Treg depletion in BALB/c DEREG mice, respectively.

RESULTS

Both mouse lines generated comparable Th2 responses, but GATA-3+ Th2 cells comprised significantly higher proportions of parasite-specific cells in the more resistant BALB/c line. In addition, BALB/c mice exhibited stronger TFH responses and more rapid differentiation of IgG1+ germinal center B cells. The superior quality of the adaptive responses was accompanied by the early expansion of Foxp3+ Treg in BALB/c mice. While B cell transfers conveyed partial resistance to primary infection in the BALB/c line, transient Treg depletion at the onset of infection neither altered the quality of the Th2 effector response nor the extent of TFH and IgG1+ B cell responses, nor the control of parasite fitness. In contrast, Th2 responses were repressed following IL-2-induced Treg expansion in C57BL/6 mice, including the further marginalization of parasite-specific responses.

CONCLUSION

Together, these results indicate that resistance to GI nematodes depends on the quality rather than the quantity of T helper cell responses.