Modulation of helper T cell function by prostaglandins

Abstract

To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transformating growth factor beta 1 by CD4+ T cells. 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. PGE2 and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, 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, TH0-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. 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 IFN gamma.