Regulation by Differential Development of Th1 and Th2 Cells in Peripheral Tolerance to Cardiac Allograft Induced by Blocking ICAM-1/LFA-1 Adhesion

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Abstract
Background Specific immune tolerance to cardiac allografts is induced by anti–ICAM-1 and anti–LFA-1 MAbs. Although the expression of the Th1 cytokines IL-2 and IFN-γ is shown to increase in association with acute rejection, the roles of cytokines in the induction of peripheral tolerance by anti–ICAM-1 and anti–LFA-1 MAbs are not yet known. Methods and Results BALB/c hearts were transplanted into C3H/He mice. The MAbs to ICAM-1 and LFA-1 were injected for 3 days after transplantation in some recipients, and others were treated with FK506. IL-2 concentration in the supernatant of splenocytes from MAb-treated mice that were mix-cultured with donor splenocytes was lower than in normal controls. The expression of Th1 cytokines, detected by Northern blot assay, was enhanced in grafts or spleens of nontreated mice, whereas Th2 cytokines were expressed in the spleens of MAb-treated mice. No cytokine expression was enhanced in mice treated with FK506. Also, the induction of tolerance was prevented by the administr...