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6340789 
Journal Article 
Deltafn2fn2tetrahydrocannabinol.-tetrahydrocannabinol suppresses macrophage costimulation by decreasing heat-stable antigen expression 
Clements, DJ; Matveyeva, M; Mccoy, KL 
1998 
Yes 
International Journal of Immunopharmacology
ISSN: 0192-0561 
Elsevier 
20 
8 
415-428 
English 
9778102 
WOS:000075968900004 
Delta9-tetrahydrocannabinol (THC) suppresses several immunologic functions of macrophages. The costimulatory activity of a THC-exposed macrophage hybridoma was investigated by its ability to elicit interleukin-2 secretion by a helper T cell hybridoma activated with immobilized monoclonal anti-CD3 antibody. THC added at culture initiation inhibited the T cell response in a dose-dependent manner. When the macrophages were fixed with paraformaldehyde before culture, THC had no effect on T cell stimulation. However, macrophages, which were preincubated with THC and then fixed, were impaired in delivering costimulatory signals to T cells cultured without THC. The drug’s inhibitory effect on macrophage costimulatory activity was reversible. THC exposure also decreased macrophage expression of heat-stable antigen (HSA). Antibody blocking experiments showed that HSA expressed on the macrophages provided an important costimulatory signal, whereas B7-1 and B7-2 molecules had a minor role. Treatment of the macrophages with phosphatidylinositol-specific phospholipase C cleaved HSA, but not the transmembrane B7 molecules, from the cell surface. Similar to THC, enzyme treatment significantly diminished macrophage costimulatory activity, which was also reversible. After drug or enzyme removal, HSA expression returned to the control level by 4 h. Therefore, THC suppresses macrophage costimulatory activity by diminishing cell surface expression of HSA. 
Delta-tetrahydrocannabinol; Immunosuppression; Macrophage function; T cell costimulation