The unique features of Th9 cells and their products

Abstract

Although it was discovered more than two decades ago, new information concerning the biological activities of IL-9 has been provided in recent years, after the isolation of cells that selectively produce this cytokine, designated "Th9." Th9 cells are generated in vitro by polarization, mainly by TGF-β and IL-4, during activation with the specific antigen, or with anti-CD3/CD28 antibodies. This review deals mainly with Th9 generated by the former, "physiological" mode of activation. Of particular interest is the unique production kinetics of IL-9: the cytokine is produced very rapidly, but after reaching its peak (day 3 in our studies), it declines sharply to trace levels. In addition to IL-9, Th9 cells also produce similar amounts of another cytokine, IL-10, but the production kinetics of these two cytokines are strikingly different. Antigen-activated Th9 in our studies also developed pathogenic capacity, but only during the short time period of peak IL-9 production. Interestingly, no IL-9-producing cells were detected in sites of inflammation induced by Th9, in contrast to Thl and Thl7. The unique features of Th9 cells and their products are discussed with regards to the known and assumed functions of the cytokine.

FIGURE 1

Production kinetics of IL-9 differs from that of other cytokines. Naïve CD4 cells of 3A9 mice were activated with HEL and APC in the presence of polarizing cytokines specific for Th9, Th2 or Th17. Cells were collected at different time points, as indicated, and intracellular expression of IL-9, IL-10, IL-4, and IL-17 was measured by flow cytometry. (A) Data of a representative experiment. (B) Mean percent of cells expressing intracellularly the indicated cytokines. This figure is modified from Ref. , with permission from the Journal of Immunology.

FIGURE 2

Assessment of Th9 cell plasticity. Th9 cells collected following 3 days of activation/polarization were expanded with IL-2 for 4 days, washed, and reactivated for 3 days with HEL and APC in the presence of polarizing cytokines specific for Th1, Th2, Th17, and Th9. Intracellular expression of IL-10, IFN-γ, IL-17, IL-4, and IL-9. A representative experiment; similar data were obtained in another experiment. This figure is modified from Ref. , with permission from the Journal of Immunology.