Modulation of helper T cell function by prostaglandins

Objective. To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-γ (IFNγ), granulocytemacrophage colony-stimulating factor, and transforming growth factor β1 by CD4+ T cells. Methods. TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E₁ (PGE₁) analog misoprostol and PGE₂. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays. Results. PGE₂ and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFNγ, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE₂ are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, THO-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells. Conclusion. Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE₂, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFNγ.