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 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.