M. Jasinski et al., ISOTYPE-SPECIFIC REGULATION OF MHC CLASS-II GENE-EXPRESSION IN HUMAN MONOCYTES BY EXOGENOUS AND ENDOGENOUS TUMOR-NECROSIS-FACTOR, Journal of clinical immunology, 15(4), 1995, pp. 185-193
The control of expression of MHC class II molecules on antigen-present
ing cells is important for the induction of immunity, while aberrant e
xpression of these molecules plays a role in the immunopathology of au
toimmune diseases. This study explored the role of tumor necrosis fact
or alpha (TNF) in controlling the level of HLA class II mRNA in human
monocytes. Exposure of monocytes to exogenous recombinant TNF (rTNF) s
electively up-regulated DR (alpha-mRNA but not DP or DQ alpha-mRNA. In
hibitors of TNF synthesis, pentoxifylline (PTX) and thalidomide, inhib
ited TNF mRNA accumulation in LPS-activated monocytes and down-regulat
ed DR mRNA but not DP or DQ mRNA. The inhibitory effect of anti-TNF mo
noclonal antibody (MAb) indicated that endogenously generated TNF acte
d extracellularly. Anti-p75 TNF-R2 receptor and to a lesser extent ant
i-p55 TNF-R1 MAbs inhibited TNF-mediated up-regulation of DR mRNA and
TNF mRNA. Taken together, this implies that endogenously generated TNF
plays a role in controlling isotype-specific MHC class II gene expres
sion in human monocytes/macrophages. These results may have some impli
cations for anti-tumor response and autoimmunity.