EFFECT OF RIFAMPIN ON CD1B EXPRESSION AND DOUBLE-NEGATIVE T-CELL RESPONSES AGAINST MYCOBACTERIA-DERIVED GLYCOLIPID ANTIGEN

Non-classical antigen-presentation by CD1 molecules expressed on cytok ine-activated monocytes (CAM), and cell-mediated responses supported b y double-negative (DN) and by CD8(+) responder alpha beta T cells, are involved in host resistance against mycobacterial infections. The CD1 b protein is responsible for presentation of non-peptide, lipid antige ns to T cells. In this context, a pivotal role is played by induction of CD1b protein on the membrane of human monocytes activated by GM-CSF alone, and more efficiently by GM-CSF combined with IL-4. Rifampin (R FP), a drug which is extensively utilized for chemoprophylaxis or trea tment of Mycobacterium tuberculosis, is known to reduce a number of B, or T cell-dependent responses. Therefore we undertook immunopharmacol ogical studies on RFP, to determine the effects of this agent on human macrophage function, relative to antigen presentation by CD1b molecul es and on DN T cell cytolytic function. The results showed that: (a) g raded concentration of RFP (2 or 10 mu g/ml) induced a significant inc rease of CD1 expression, in CAM as evaluated by FAGS analysis;.(b) RFP increased significantly the specific mAb binding to CD1 on CAM surfac e; (c) treatment of effector cells with RFP did not reduce DN T cell-m ediated cytolysis against lymphoblastoid cells transfected with CD1b c DNA (C1R.b6 cells), pulsed with IM. tuberculosis. These results sugges t that RFP could be of potential value in improving mycobacterial anti gen presentation without impairing responder T cell function.