Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process

The accessory function of antigen-presenting cells depends on the presence of a number of costimulatory molecules, including members of the B7 family (CD80 and CD86) and the CD5 coligand CD72. The aim of this study was to eva luate the regulation of T cell-antigen-presenting cell, costimulatory pathw ays in the lung of patients with a typical Th1-type reaction, i.e., sarcoid osis. Although normal alveolar macrophages (AMs) did not bear or bore low l evels of costimulatory molecules, AMs from sarcoid patients with CD4 T-cell alveolitis upmodulated CD80, CD86, and CD72 and expressed high levels of i nterleukin (IL)-15; lymphocytes accounting for T-cell alveolitis expressed Th1-type cytokines [interferon (IFN)-gamma and/or IL-2] and bore high level s of CD5 and CD28 but not of CD152 molecules. In vitro stimulation of AMs w ith Th1-related cytokines (IL-15 and IFN-gamma) upregulated the expression of CD80 and CD86 molecules. However, stimulation with IL-15 induced the exp ression of Th1-type cytokines (IFN-gamma) and CD28 on sarcoid T cells, sugg esting a role for this macrophage-derived cytokine in the activation oft;he sarcoid T-cell pool. The hypothesis that CD80 and CD86 molecules regulate the sarcoid T-cell response was confirmed by the evidence that AMs induced a strong proliferation of T cells that was inhibited by pretreatment with C D80 and CD86 monoclonal antibodies. To account for these data, it is propos ed that locally released cytokines provide AMs with accessory properties th at contribute to the development of sarcoid T-cell alveolitis.