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 cytokine-activated monocytes (CAM), and cell-mediated responses supported by double-negative (DN) and by CD8+ responder alphabeta T cells, are involved in host resistance against mycobacterial infections. The CD1b protein is responsible for presentation of non-peptide, lipid antigens 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 (RFP), a drug which is extensively utilized for chemoprophylaxis or treatment of Mycobacterium tuberculosis, is known to reduce a number of B, or T cell-dependent responses. Therefore we undertook immunopharmacological studies on RFP, to determine the effects of this agent on human macrophage function, relative to antigen presentation by CD1b molecules and on DN T cell cytolytic function. The results showed that: (a) graded concentration of RFP (2 or 10 microg/ml) induced a significant increase of CD1b expression, in CAM as evaluated by FACS analysis; (b) RFP increased significantly the specific mAb binding to CD1b on CAM surface; (c) treatment of effector cells with RFP did not reduce DN T cell-mediated cytolysis against lymphoblastoid cells transfected with CD1b cDNA (C1R.b6 cells), pulsed with M. tuberculosis. These results suggest that RFP could be of potential value in improving mycobacterial antigen presentation without impairing responder T cell function.
Giuliani
A
A
Department of Neurosciences, University of Rome Tor Vergata, Italy.
Porcelli
S A
SA
Tentori
L
L
Graziani
G
G
Testorelli
C
C
Prete
S P
SP
Bussini
S
S
Cappelletti
D
D
Brenner
M B
MB
Bonmassar
E
E
Aquino
A
A
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018949:Antigens, CD1 / Q000096:biosynthesis*; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D006017:Glycolipids / Q000276:immunology*; D006801:Humans; D007202:Indicators and Reagents; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology*; D012293:Rifampin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000904:Antibiotics, Antitubercular; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D006017:Glycolipids; D007202:Indicators and Reagents; D012293:Rifampin