IL-2 and autocrine IL-4 drive the in vivo development of antigen-specific Th2 T cells elicited by nematode parasites.
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.
Liu
Zhugong
Z
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Liu
Qian
Q
Hamed
Hossein
H
Anthony
Robert M
RM
Foster
Anthony
A
Finkelman
Fred D
FD
Urban
Joseph F
JF
Gause
William C
WC
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D019898:Autocrine Communication / Q000235:genetics / Q000276:immunology*; D024201:Bystander Effect / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009559:Nippostrongylus / Q000276:immunology*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D019138:Antibodies, Blocking; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007376:Interleukin-2; D015847:Interleukin-4