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Mismatched Antigen Prepares T Cells for Suppression of Airway Hyperresponsiveness¹

Niyun Jin^2,*, Christian Taube^2,, Laura Sharp^*, Youn-Soo Hahn^*,, Xiang Yin^*, J. M. Wands^*, Christina L. Roark^*, Rebecca L. O’Brien^*, Erwin W. Gelfand and Willi K. Born^3,*

^* Department of Immunology and Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206; and Department of Pediatrics, Chungbuk National University and College of Medicine, Heungdeok-Gu, Korea

T cells suppress airway hyperresponsiveness (AHR) induced in allergen-challenged mice but it is not clear whether the suppression is allergen specific. The AHR-suppressive cells express TCR-V4. To test whether the suppressive function must be induced, we adoptively transferred purified V4⁺ cells into T cell-deficient and OVA-sensitized and -challenged recipients (B6.TCR-V4^–/–/6^–/–) and measured the effect on AHR. V4⁺ T cells isolated from naive donors were not AHR-suppressive, but V4⁺ cells from OVA-stimulated donors suppressed AHR. Suppressive V4⁺ cells could be isolated from lung and spleen. Their induction in the spleen required sensitization and challenge. In the lung, their function was induced by airway challenge alone. Induction of the suppressors was associated with their activation but it did not alter their ability to accumulate in the lung. V4⁺ T cells preferentially express V4 and -5 but their AHR-suppressive function was not dependent on these Vs. Donor sensitization and challenge not only with OVA but also with two unrelated allergens (ragweed and BSA) induced V4⁺ cells capable of suppressing AHR in the OVA-hyperresponsive recipients, but the process of sensitization and challenge alone (adjuvant and saline only) was not sufficient to induce suppressor function, and LPS as a component of the allergen was not essential. We conclude that AHR-suppressive V4⁺ T cells require induction. They are induced by allergen stimulation, but AHR suppression by these cells does not require their restimulation with the same allergen.

This article has been cited by other articles:

				L. Cook, N. Miyahara, N. Jin, J. M. Wands, C. Taube, C. L. Roark, T. A. Potter, E. W. Gelfand, R. L. O'Brien, and W. K. Born Evidence That CD8+ Dendritic Cells Enable the Development of {gamma}{delta} T Cells That Modulate Airway Hyperresponsiveness J. Immunol., July 1, 2008; 181(1): 309 - 319. [Abstract] [Full Text] [PDF]

				N. Jin, N. Miyahara, C. L. Roark, J. D. French, M. K. Aydintug, J. L. Matsuda, L. Gapin, R. L. O'Brien, E. W. Gelfand, and W. K. Born Airway Hyperresponsiveness through Synergy of {gamma}{delta} T Cells and NKT Cells J. Immunol., September 1, 2007; 179(5): 2961 - 2968. [Abstract] [Full Text] [PDF]