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 have been compared with positive Kveim tests and the sites of PPD injection in sarcoid patients. Monoclonal antibodies have been used in indirect immunofluorescence often in combination with histochemical methods for the detailed characterization of the cells involved. The antibodies used included two 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 centre, predominantly HLA-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.