Impaired antigen-presenting cell function contributes to T-cell hyporesponsiveness in stable lung transplant recipients

Background. Peripheral blood mononuclear cells (PBMC) of stable renal or ca rdiac transplant recipients were previously shown to respond to allogeneic cells but not to soluble protein antigens, The aim of the present study was to assess the T-cell and antigen-presenting cell (APC) functions of stable lung transplant (LT) recipients. Methods, We obtained PBMC from 38 stable LT recipients. PBMC from healthy v olunteers served as controls. PBMC were stimulated with either anti-CD3 mon oclonal antibody, allogeneic PBMC, or tetanus toroid (TT), T-cell activatio n was assessed by determination of interleukin (IL)-2 levels in culture sup ernatants; in some experiments, interferon-gamma levels were also determine d. Patients' APC function was tested in a mixed leukocyte reaction using pa tients' PBMC as stimulators. The expression of class II MHC, B7.2, and CD40 molecules on patients' APC was determined by flow cytometry, and their pro duction of IL-10 and IL-12 at the basal state and upon CD40 ligation was al so measured. Results. Patients' T cells produced normal amounts of IL-2 in response to a nti-CD3 monoclonal antibody and allogeneic PBMC, In contrast, the response of memory T cells to TT was severely blunted both in terms of IL-2 and inte rferon-gamma production. Patients' PBMC were poor stimulators in mixed leuk ocyte reaction, and class II MHC expression on patients' monocytes was sign ificantly reduced. Patients' APC presented a modest but significant increas e in basal IL-10 production and produced significantly less IL-12 upon CD40 ligation than control APC. Conclusions. T cells from stable LT recipients respond normally to stimuli that do not depend on autologous APC. The major impairment in the T-cell re sponse to TT is caused by APC dysfunction, which involves decreased class I I MHC expression and deficient IL-12 synthesis.