IL-2 and Autocrine IL-4 Drive the in Vivo Development of Antigen-specific Th2 T Cells Elicited by Nematode Parasites

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2005 Feb 9

PMID 15699158

Citations 26

Authors

Zhugong Liu

Qian Liu

Hossein Hamed

Robert M Anthony

Anthony Foster

Fred D Finkelman

Joseph F Urban Jr

William C Gause

Affiliations

Soon will be listed here.

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.

Citing Articles

Site-specific regulation of Th2 differentiation within lymph node microenvironments.

Lyons-Cohen M, Shamskhou E, Gerner M J Exp Med. 2024; 221(4).

PMID: 38442268 PMC: 10912907. DOI: 10.1084/jem.20231282.

Trichinella spiralis -induced immunomodulation signatures on gut microbiota and metabolic pathways in mice.

Sun X, Hao C, Wu A, Luo Z, El-Ashram S, Alouffi A PLoS Pathog. 2024; 20(1):e1011893.

PMID: 38166140 PMC: 10786400. DOI: 10.1371/journal.ppat.1011893.

Microbial Components and Effector Molecules in T Helper Cell Differentiation and Function.

Lee C, Lee H, Park J, Im S Immune Netw. 2023; 23(1):e7.

PMID: 36911805 PMC: 9995987. DOI: 10.4110/in.2023.23.e7.

Initiation of type 2 immunity at barrier surfaces.

McDaniel M, Lara H, von Moltke J Mucosal Immunol. 2023; 16(1):86-97.

PMID: 36642383 PMC: 10290812. DOI: 10.1016/j.mucimm.2022.11.002.

Monocytes maintain central nervous system homeostasis following helminth-induced inflammation.

Peng J, Sy C, Ponessa J, Lemenze A, Hernandez C, Inclan-Rico J Proc Natl Acad Sci U S A. 2022; 119(37):e2201645119.

PMID: 36070344 PMC: 9478671. DOI: 10.1073/pnas.2201645119.

References

Noben-Trauth N, Hu-Li J, Paul W . IL-4 secreted from individual naive CD4+ T cells acts in an autocrine manner to induce Th2 differentiation. Eur J Immunol. 2002; 32(5):1428-33. DOI: 10.1002/1521-4141(200205)32:5<1428::AID-IMMU1428>3.0.CO;2-0. View

Launois P, Gumy A, Himmelrich H, Locksley R, Rocken M, Louis J . Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at the onset of infection with Leishmania major instructs Th2 cell development, resulting.... J Immunol. 2002; 168(9):4628-35. DOI: 10.4049/jimmunol.168.9.4628. View

Liu Z, Liu Q, Pesce J, Whitmire J, Ekkens M, Foster A . Nippostrongylus brasiliensis can induce B7-independent antigen-specific development of IL-4-producing T cells from naive CD4 T cells in vivo. J Immunol. 2002; 169(12):6959-68. DOI: 10.4049/jimmunol.169.12.6959. View

Shinkai K, Mohrs M, Locksley R . Helper T cells regulate type-2 innate immunity in vivo. Nature. 2002; 420(6917):825-9. DOI: 10.1038/nature01202. View

Szabo S, Sullivan B, Peng S, Glimcher L . Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol. 2002; 21:713-58. DOI: 10.1146/annurev.immunol.21.120601.140942. View

Lohr J, Knoechel B, Jiang S, Sharpe A, Abbas A . The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat Immunol. 2003; 4(7):664-9. DOI: 10.1038/ni939. View

Kelly B, Stetson D, Locksley R . Leishmania major LACK antigen is required for efficient vertebrate parasitization. J Exp Med. 2003; 198(11):1689-98. PMC: 2194132. DOI: 10.1084/jem.20031162. View

Cote-Sierra J, Foucras G, Guo L, Chiodetti L, Young H, Hu-Li J . Interleukin 2 plays a central role in Th2 differentiation. Proc Natl Acad Sci U S A. 2004; 101(11):3880-5. PMC: 374338. DOI: 10.1073/pnas.0400339101. View

Voehringer D, Shinkai K, Locksley R . Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity. 2004; 20(3):267-77. DOI: 10.1016/s1074-7613(04)00026-3. View

10.

Nelson B . IL-2, regulatory T cells, and tolerance. J Immunol. 2004; 172(7):3983-8. DOI: 10.4049/jimmunol.172.7.3983. View

11.

Eisenbarth S, Zhadkevich A, Ranney P, Herrick C, Bottomly K . IL-4-dependent Th2 collateral priming to inhaled antigens independent of Toll-like receptor 4 and myeloid differentiation factor 88. J Immunol. 2004; 172(7):4527-34. DOI: 10.4049/jimmunol.172.7.4527. View

12.

Marinari B, Costanzo A, Marzano V, Piccolella E, Tuosto L . CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters. Proc Natl Acad Sci U S A. 2004; 101(16):6098-103. PMC: 395929. DOI: 10.1073/pnas.0308688101. View

13.

Thornton A, Donovan E, Piccirillo C, Shevach E . Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol. 2004; 172(11):6519-23. DOI: 10.4049/jimmunol.172.11.6519. View

14.

Mendez S, Reckling S, Piccirillo C, Sacks D, Belkaid Y . Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med. 2004; 200(2):201-10. PMC: 2212012. DOI: 10.1084/jem.20040298. View

15.

de la Rosa M, Rutz S, Dorninger H, Scheffold A . Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol. 2004; 34(9):2480-8. DOI: 10.1002/eji.200425274. View

16.

Min B, Prout M, Hu-Li J, Zhu J, Jankovic D, Morgan E . Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite. J Exp Med. 2004; 200(4):507-17. PMC: 2211939. DOI: 10.1084/jem.20040590. View

17.

Liu Z, Liu Q, Pesce J, Anthony R, Lamb E, Whitmire J . Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo. Immunol Rev. 2004; 201:57-74. DOI: 10.1111/j.0105-2896.2004.00186.x. View

18.

NOELLE R, Krammer P, OHara J, UHR J, Vitetta E . Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984; 81(19):6149-53. PMC: 391877. DOI: 10.1073/pnas.81.19.6149. View

19.

Finkelman F, OHara J, Goroff D, Smith J, Villacreses N, Mond J . Production of BSF-1 during an in vivo, T-dependent immune response. J Immunol. 1986; 137(9):2878-85. View

20.

Smith K . Interleukin-2: inception, impact, and implications. Science. 1988; 240(4856):1169-76. DOI: 10.1126/science.3131876. View