Allergic airway hyperresponsiveness-enhancing γδ T cells develop in normal untreated mice and fail to produce IL-4/13, unlike Th2 and NKT cells

Niyun Jin, Christina L. Roark, Nobuaki Miyahara, Christian Taube, M. Kemal Aydintug, J. M. Wands, Yafei Huang, Youn Soo Hahn, Erwin W. Gelfand, Rebecca L. O'Brien, Willi K. Born

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing and inhibitory γδ T cells. The AHR-enhancing cells belong to the Vγ1+ γδ T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSAhigh maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-γ, TNFRp75, or IL-4 did not produce these AHR-enhancing γδ T cells, but in the absence of IFN-γ, spontaneous development of these cells was restored by adoptive transfer of IFN-γ-competent dendritic cells from untreated donors. The i.p. injection of OVA/aluminum hydroxide restored development of the AHR enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-γ, or IL-4 to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing γδ T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR.

Original languageEnglish
Pages (from-to)2002-2010
Number of pages9
JournalJournal of Immunology
Volume182
Issue number4
DOIs
Publication statusPublished - Feb 15 2009
Externally publishedYes

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Th2 Cells
Natural Killer T-Cells
Interleukin-13
Interleukin-4
T-Lymphocytes
Aluminum Hydroxide
Adoptive Transfer
Interleukin-5
T-Lymphocyte Subsets
Thymocytes
Allergens
Dendritic Cells
Cytokines
Injections
Population

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Allergic airway hyperresponsiveness-enhancing γδ T cells develop in normal untreated mice and fail to produce IL-4/13, unlike Th2 and NKT cells. / Jin, Niyun; Roark, Christina L.; Miyahara, Nobuaki; Taube, Christian; Aydintug, M. Kemal; Wands, J. M.; Huang, Yafei; Hahn, Youn Soo; Gelfand, Erwin W.; O'Brien, Rebecca L.; Born, Willi K.

In: Journal of Immunology, Vol. 182, No. 4, 15.02.2009, p. 2002-2010.

Research output: Contribution to journalArticle

Jin, N, Roark, CL, Miyahara, N, Taube, C, Aydintug, MK, Wands, JM, Huang, Y, Hahn, YS, Gelfand, EW, O'Brien, RL & Born, WK 2009, 'Allergic airway hyperresponsiveness-enhancing γδ T cells develop in normal untreated mice and fail to produce IL-4/13, unlike Th2 and NKT cells', Journal of Immunology, vol. 182, no. 4, pp. 2002-2010. https://doi.org/10.4049/jimmunol.0803280
Jin, Niyun ; Roark, Christina L. ; Miyahara, Nobuaki ; Taube, Christian ; Aydintug, M. Kemal ; Wands, J. M. ; Huang, Yafei ; Hahn, Youn Soo ; Gelfand, Erwin W. ; O'Brien, Rebecca L. ; Born, Willi K. / Allergic airway hyperresponsiveness-enhancing γδ T cells develop in normal untreated mice and fail to produce IL-4/13, unlike Th2 and NKT cells. In: Journal of Immunology. 2009 ; Vol. 182, No. 4. pp. 2002-2010.
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abstract = "Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing and inhibitory γδ T cells. The AHR-enhancing cells belong to the Vγ1+ γδ T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSAhigh maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-γ, TNFRp75, or IL-4 did not produce these AHR-enhancing γδ T cells, but in the absence of IFN-γ, spontaneous development of these cells was restored by adoptive transfer of IFN-γ-competent dendritic cells from untreated donors. The i.p. injection of OVA/aluminum hydroxide restored development of the AHR enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-γ, or IL-4 to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing γδ T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR.",
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AU - Aydintug, M. Kemal

AU - Wands, J. M.

AU - Huang, Yafei

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