Abstract

143 In vitro peripheral blood mononuclear cells (PBMCs) of stable transplant recipients respond to polyclonal activation, but not to soluble protein antigens (ag), which have to be processed and presented by self antigen presenting cells (APCs). The aim of the present study was to assess APC function in stable lung transplant (LT) recipients and to elucidate whether defective response to soluble ag is due to T cell or APC dysfunction. We obtained PBMCs from 29 stable LT recipients with normal pulmonary function a mean of 3 years after transplantation. Patients received a triple CsA-based immunosuppressive regimen. We also obtained PBMCs from 29 healthy volunteers, which served as controls. LT recipients' and control PBMCs were stimulated with a) allogeneic PBMCs, b) anti-CD3 monoclonal antibody (mAb), c) tetanus toxoid (TT) ± anti-CD28 mAb. APC function of patients' PBMCs was tested in a mixed leukocyte reaction (MLR) using patients' PBMCs as stimulators and control PBMCs as responders. The readout for these experiments was IL-2 production in culture supernatants. APC expression of MHC class II, B7.1, B7.2 and CD40 molecules was determined by flow cytometry. Finally, APC production of IL-10 and IL-12 in response to stimulation with CD40-L transfected fibroblasts was assessed. Patients' T cells produced normal amounts of IL-2 in response to allogeneic PBMCs (500 ± 259 vs 397 ± 236 pg/ml in controls; P = NS) and anti-CD3 mAb (2685 ± 1380 vs 1817 ± 1380 pg/ml in controls; P = NS). Response to TT was completely blunted (203 ± 270 vs 604 ± 574 pg/ml in controls; P < 0.0001) and could not be restored by providing costimulation with anti-CD28 mAb. Patients' APCs were poor stimulators in MLR and this was correlated with a drastic downregulation of MHC class II expression (median fluorescence intensity: 275 ± 66 vs 931 ± 163 in controls; P < 0.0001). Patients' APCs also produced significantly less IL-10 and IL-12 than control APCs subsequent to CD40 engagement. In conclusion, stable LT recipients' T cells cannot be activated in vitro by soluble ag such as TT. Deficient ag presentation by dysfunctional APCs probably contributes to this defect.

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