THE DISTRIBUTION OF LYMPHOID AND MACROPHAGE LIKE CELL SUBSETS OF SARCOID AND KVEIM GRANULOMATA - POSSIBLE MECHANISM OF NEGATIVE PPD REACTION IN SARCOIDOSIS

Abstract

Immunohistological observations of lymphoid and non-lymphoid cell subsets in biopsies of sarcoid skin granulomas were compared with positive Kveim tests and the sites of PPD [purified protein derivative] injection in sarcoid patients. Monoclonal antibodies were used in indirect immunofluorescence often in combination with histochemical methods for the detailed characterization of the cells involved. The antibodies used included 2 new reagents RFD-1 and RFD-2, which react with interdigitating cells and acid phosphatase positive macrophages, respectively. Sarcoid granulomas had a distinctive pattern of organization though there was a heterogeneity of macrophage-like and T lymphoid cells. In the center, predominantly HLS-DR+, acid phosphatase positive macrophages (RFD-2+) were seen and the lymphoid cells were almost exclusively T4+. At the periphery of the granulomas the HLA-DR+ dendritic cells were ACP negative and RFD-1+. Here T8+ cells were admixed with the T4+ population. The Kveim granuloma had fewer RFD-2+ macrophages and therefore the RFD-1+ cells were more evenly distributed, but the other cells showed a similar distribution to the established lesions. The PPD injection sites contained fewer T cells than the normal control infiltrates in PPD positive healthy individuals. The T4+/T8+ ratios were about 3:2. The most likely explanation for the PPD anergy in sarcoidosis is the sluggish traffic of T4+ cells which could be due to the sequestration of T4+ cells in sites of ongoing inflammation.