Rifampin increases cytokine-induced expression of the CD1b molecule in human peripheral blood monocytes.
In recent years, it has been shown that a nonclassical, major histocompatibility complex-independent system (i.e., CD1-restricted T-cell responses) is involved in T-cell immunity against nonpeptide antigens. The CD1 system appears to function by presenting microbial lipid antigens to specific T cells, and the antigens so far identified include several known constituents of mycobacterial cell walls. Among the four known human CD1 isoforms, the CD1b protein is the best characterized with regard to its antigen-presenting function. Expression of CD1b is upregulated on human blood monocytes upon exposure to granulocyte/macrophage-colony stimulating factor, alone or in combination with interleukin-4 (IL-4) (S. A. Porcelli, Adv. Immunol. 59:1-98, 1995). Rifampin (RFP) and its derivatives are widely used for chemoprophylaxis or chemotherapy against Mycobacterium tuberculosis. However, this agent was found to reduce the mitogen responsiveness of human B and T lymphocytes, chemotaxis, and delayed-type hypersensitivity. The present study extends the immunopharmacological profile of RFP by examining its effects on CD1b expression by human peripheral blood monocytes exposed to GM-CSF plus IL-4. The results showed that clinically attainable concentrations (i.e., 2 or 10 microg/ml for 24 h) of the agent produced a marked increase in CD1b expression on the plasma membrane, as evaluated by fluorescence-activated cell sorter analysis, whereas it had no effect on cytosolic fractions, as indicated by Western blot analysis. This was found to be the result of increased CD1b gene expression, as shown by Northern blot analysis of CD1b mRNA. These results suggest that RFP could be of potential value in augmenting the CD1b-restricted antigen recognition system, thereby enhancing protective cellular immunity to M. tuberculosis.
Tentori
L
L
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Graziani
G
G
Porcelli
S A
SA
Sugita
M
M
Brenner
M B
MB
Madaio
R
R
Bonmassar
E
E
Giuliani
A
A
Aquino
A
A
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D018949:Antigens, CD1 / Q000187:drug effects* / Q000378:metabolism; D018890:Chemoprevention; D003600:Cytosol / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*
D000904:Antibiotics, Antitubercular; D018949:Antigens, CD1; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012293:Rifampin