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Infections with GI nematodes are cleared with different kinetics depending on the host genotype. SJL mice rapidly promote antibody responses and terminate infection with the small intestinal nematode H. polygyrus within three weeks despite the generation of rather limited Th2 effector cell responses. As this is contrasting with the accumulation of large numbers of GATA-3+ Th2 cells in more susceptible BALB/c and C57BL/6 mice, we asked which factors drive this type of response.
The extent of GATA-3+ T cell expansion determined in SJL, BALB/c and C57BL/6 mice correlated strongly with IFN-g production by CD4+ and CD8+ T cells early during H. polygyrus infection. Limited IFN-g responses and restricted Th2 expansion coincided with high frequencies of Foxp3+ Treg in lymphatic organs of SJL mice. Conversely, the stronger IFN-g production ensuing the partial removal of Foxp3+Treg as well as the supplementation with recombinant IFN-g further promoted the expansion of GATA-3+ T cells in BALB/c mice. Next to high numbers of regulatory T cells, SJL mice harbored exceptionally few NK cells in the spleen and those produced little IFN-g in response to IL-12/IL-18. Furthermore, the frequencies of Treg and NK cells as wells as the IFN-g profiles of CD4+ and CD8+ T cells matched the patterns of Th2 expansion in (BL/6 x SJL) F2 mice infected with H. polygrus.
In summary, IFN-g released by NK and effector/memory T cells seems to support rather than impair the generation of GATA-3+ effector T cells in H. polygyrus infection. Whether the activity of NK cells or the less stringent control of effector responses by Treg deviate the anti-nematode response in favor of effector cells and thereby promote susceptibility is under current investigation.