Reversal of established delayed type hypersensitivity reactions following therapy with IL-4 or antigen-specific Th2 cells

Delayed-type hypersensitivity reactions (DTHR) are mediated by IFN-gamma -p roducing CD4(+) (Th1) or CD8(+) T cells (Tc1) and can be prevented by steer ing T cells toward an IL-4-producing Th2 or Tc2 phenotype. It is currently accepted that T cells can be directed toward a Th2 or Tc2 phenotype only du ring the initiation of an immune response. Once established, the cytokine p attern of immune reactions is believed to be stable. Therefore, inhibition of DTHR by the induction of Th2/Tc2 responses, termed immune deviation, is considered only as a prevention but not as a therapy of harmful DTHR. Here we demonstrate that therapeutic immune deviation can reverse established co ntact hypersensitivity (CHS), a Th1/Tc1-mediated DTHR. One or two weeks aft er induction of CHS, mice received either a single cycle of IL-4 therapy or adoptive transfer of antigen-specific Th2 cells. This treatment generated a novel state of immunity that provided long-lasting protection against tis sue destruction and neutrophil recruitment during subsequent antigen exposu res. Therapeutic immune deviation of established CHS was dependent on CD4() T cells and the induction of endogenous IL-4 synthesis. Thus, a populatio n of immunoregulatory Th2 cells persists during advanced inflammatory respo nses that can be used for therapeutic deviation of established DTHR.