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Lindsey F. Nugent, Cuiyan Tan, Mehak Aziz, Barbara P. Vistica, Guangpu Shi, Igal Gery; Antigen-Specific Th9 Cells are Unique in their Cytokine Kinetics, Plasticity and Retention at the Inflammatory Site. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3011.
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We previously reported data concerning the generation and unique features of Th9 cell lines selectively expressing IL-9. Here, we extended the analysis of these cells.
Naïve CD4+ cells isolated from hen egg lysozyme (HEL)-specific TCR transgenic mice were activated by HEL and polarized toward IL-9 production by IL-4 and TGF-beta. For reactivation, these cells were expanded with IL-2 and restimulated with HEL in Th9 polarizing medium. Plasticity of Th9 was examined by restimulating in media polarizing for Th1, Th2, or Th17. ELISA and intracellular staining were used to measure cytokine production. Real-time PCR was used to measure mRNA transcript levels. For adoptive transfer, Th9 cells were injected into naïve HEL-Tg mice. Recipients were sacrificed and their eyes, spleens and peripheral blood were collected for recovery of donor cells.
(i) Th9 cells resemble other Th lineages by their faster and stronger response to restimulation. (ii) The kinetics of IL-9 production by Th9 lines differed greatly from the kinetics of signature cytokine production by Th2 (IL-4) and Th17 (IL-17) cell lines. IL-9 expression sharply increased on day 3, and steeply declined on day 4, whereas the expression of all other cytokines increased gradually, with the highest expression level on day 6. (iii) Th9 cells exhibited moderate levels of plasticity when cultured in media polarizing towards Th1 and Th17. Th9 cultures polarized towards Th2, however, massively switched to producing IL-4. (iv) When adoptively transferred to recipients expressing HEL in the eyes, IL-9 producing donor cells were detected in the blood but not their inflamed eyes, suggesting that exposure to HEL in these eyes arrested the IL-9 production in Th9 cells.
Collectively, these data provide new information concerning Th9 cells and reveal their uniqueness, in particular with regard to their response to restimulation, plasticity and retention of these cells in affected target tissues.
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