Enhanced alveolar macrophage-mediated antigen-induced T-lymphocyte proliferation in sarcoidosis.

Abstract

Expansion of T-lymphocyte numbers is a characteristic feature of the alveolitis of pulmonary sarcoidosis. One mechanism that may influence the numbers of T-lymphocytes in the lung is the process of antigen presentation in which alveolar macrophages, in the presence of antigen, induce T-lymphocytes to replicate. To evaluate this process in sarcoidosis, alveolar macrophages were obtained by bronchoalveolar lavage, pulsed with tetanus toxoid, and co-cultured with purified autologous T cells. Strikingly, antigen-pulsed alveolar macrophages from sarcoid patients induced more than a twofold increase in autologous T-lymphocyte proliferation compared with the response seen using cells from normals or patients with idiopathic pulmonary fibrosis (P < 0.0001, all comparisons). In contrast, when monocytes were used as the antigen presenting cell, no significant differences were observed in T cell proliferation induced by antigen among the three groups. The enhanced T-lymphocyte proliferation induced by sarcoid alveolar macrophages was not dependent on the compartment from which the T cells were derived, and was independent of the specific antigen used. One possible explanation for augmented antigen presentation seen in sarcoid is that an increased percentage of sarcoid alveolar macrophages express HLA-DR or HLA-DS surface antigens. However, most normal and sarcoid alveolar macrophages express HLA-DR and HLA-DS surface antigens, and the percentage of macrophages expressing these antigens was not significantly different in the two groups. Thus, while the mechanisms of the enhanced antigen presentation in the sarcoid lung are unknown, the process of antigen-driven, alveolar macrophage-modulated lung T cell proliferation may explain, at least in part, the expansion of lung T-lymphocyte numbers that characterizes this disease.

In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases

“…It remains speeulative whether this was due to biologieal or technical reasons. Only little IFN-y may be produced in the alveolar spaces in vivo due to the immunosuppressive effect of surfactant [36,37] or the poor antigen-presenting function of alveolar macrophages [38] assoeiated with their release of suppressor factors [39]. Locally produced IFN-y may also be bound to receptors [40] or inactivated by an inhibitor or proteases [41].…”

Increased CD11/CD18 expression on peripheral blood leucocytes of patients with sarcoidosis

“…Before their migration to sites of active disease [7,8] sarcoid mononuclear cells must adhere to the endothelium of capillaries. Once within tissues, sarcoid lymphocytes and monocytes have been shown to associate closely [9,10], an interaction which may favour both granuloma formation [11] and the enhanced lymphoproliferation which has been reported by cells retrieved from tissues such as the lung [10,12].…”

Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes

“…Alveolar macrophages (AM) from patients with sarcoidosis have been reported to present reeall antigen to T lymphocytes as effectively as autologous peripheral blood monocytes (Venet et al, 1985), In contrast, alveolar macrophages (AM) from normal subjects are considered to be ineffective in this respect (Toews et al, 1984;Ferro et al, 1987), The reasons for this substantial difference in accessory cell function are unclear. By ultrastructural criteria, sarcoid AM are morphologieally abnormal (Danel et al, 1983); phenotypically and biochemically they appear to be less mature than normal AM (Gant & Hamblin, 1985;Hanee et al, 1985;Barth et al, 1988); their vitamin D3 metabolism may influenee maerophage differentiation (Adams et al, 1983), The expression of HLA-DR, Class II MHC antigens on sarcoid AM is only slightly greater than that of normal AM, whilst that of HLA-DQ is considerably increased (Campbell et al, 1986;Agostini et al, 1987;Haslam, Parker & Townsend, 1990;Spurzem et al, 1990), It is unclear to what extent these characteristics of sarcoid AM contribute to their enhanced antigen-presenting capacity.…”