Abstract
The intestinal nematode parasite, Nippostrongylus brasiliensis, triggers potent type 2 immunity. Using OVA peptide as a model Ag, we have examined the adjuvant effects of this parasite on the in vivo development of Ag-specific Th2 cells from naive DO11.10 T cells. Our findings show that Th2 cells can develop from transferred naive OVA-specific DO11.10 T cells in recipient IL-4-/- mice inoculated with N. brasiliensis plus OVA. However, autocrine IL-4 is required for in situ Th2 cell differentiation since transferred IL-4Ralpha-deficient DO11.10 T cells showed greatly reduced Th2 cell development in inoculated IL-4-/- recipient mice. Surprisingly, we also found that IL-2 blockade promoted B7-dependent T cell cycling, but inhibited the development of OVA-specific Th2 cells. Furthermore, the effects of IL-2 occurred independently of CD25+ T regulatory cells. These studies establish a previously unrecognized requirement for autocrine IL-4 and IL-2 in Th2 responses elicited by nematode parasites.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Blocking / administration & dosage
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Autocrine Communication / genetics
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Autocrine Communication / immunology*
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Bystander Effect / genetics
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Bystander Effect / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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Cell Cycle / genetics
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Cell Cycle / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Epitopes, T-Lymphocyte / immunology*
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Female
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Growth Inhibitors / administration & dosage
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / immunology
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Interleukin-2 / physiology*
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Interleukin-4 / biosynthesis
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Interleukin-4 / deficiency
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Interleukin-4 / genetics
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Interleukin-4 / physiology*
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Kinetics
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Nippostrongylus / immunology*
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Resting Phase, Cell Cycle / genetics
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Resting Phase, Cell Cycle / immunology
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Th2 Cells / cytology
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Th2 Cells / immunology*
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Th2 Cells / parasitology*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Antibodies, Blocking
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Epitopes, T-Lymphocyte
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Growth Inhibitors
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Interleukin-2
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Interleukin-4