B. Mytar et al., MONOCYTE-MEDIATED REGULATION OF ANTIGEN-DRIVEN IFNGAMMA PRODUCTION BYT-CELLS - THE ROLE OF ENDOGENOUSLY PRODUCED TNF, Immunological investigations, 24(6), 1995, pp. 897-906
The question was asked whether tumour necrosis factor alpha (TNF) is i
nvolved in regulation of interferon gamma (IFNgamma) production by T c
ells. Monocytes were exposed to exogenous TNF or to TNF synthesis inhi
bitors (pentoxifylline, PTX and adriamycin, ADR) and then used as anti
gen (PPD) presenting cells for autologous T cells. The ability of T ly
mphocytes to release IFNgamma was assessed after 3 days of culture. Pr
eincubation of monocytes with rTNF enhanced their ability to induce IF
Ngamma production while TNF synthesis inhibitors decreased it. Anti-TN
F and anti-TNF-R2 monoclonal antibodies (mAbs) inhibited monocyte abil
ity to present PPD for IFNgamma production which suggested that endoge
nously produced TNF by monocytes had to be released and acted on TNF-R
2 on the monocyte surface. The enhancing effect of exogeneous TNF was
also abrogated by anti-TNF-R2 mAb. Pretreatment of monocytes with rTNF
enhanced, while pretreatment with PTX decreased, PPD-induced IL-6 pro
duction. An increased production of IL-4 was found in cultures of PTX
- treated, PPD-pulsed monocytes with T cells. This may indicate that i
n the relative absence of monocyte costimulatory signal(s), probably I
L-6, Th, cells are stimulated. These results indicate that TNF is invo
lved in control of monocyte-mediated regulation of cytokine production
by T cells.