ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Normal immune homeostasis is regulated partly by a small population of CD4+ T cells that react to autologous major histocompatibility complex class-II molecules on self-cells. Decreased autoreactive T-cell responses are associated with cancer. Tumour growth causes syngeneic macrophages (Mø) to suppress autoreactive T-cell proliferation by decreasing Mø class-II expression and increasing Mø production of the suppressor molecule prostaglandin E2 (PGE2). Because interferon-γ (IFN-γ) is a potent Mø activation molecule which regulates both Mø PGE2 and class-II expression, the effects of IFN-γ on tumour-induced suppression of autoreactive T-cell proliferation were investigated. Exogenous IFN-γ increased normal host (NH) CD4+ autoreactive T-cell proliferation stimulated by syngeneic NHMø but decreased proliferation stimulated by tumour-bearing host (TBH) Mø. Antibody (Ab) neutralization of endogenous IFN-γ activity reduced TBH Mø-mediated suppression. Kinetic studies showed that endogenous IFN-γ suppressor activity was not exclusive during T-cell activation. Indomelhacin treatment blocked IFN-γ-induced suppression in TBH Mø-T cell cultures. TBH Mø-T cell cultures contained significantly more PGE2 than those containing NH Mø. Exogenous IFN-γ increased early PGE2 production in TBH Mø cultures but decreased production in NHMø cultures. The Ab-mediated neutralization of endogenous transforming growth factor-β or tumour necrosis factor-x reduced TBH Mμ-mediated suppression and blocked IFN-γ-induced suppression. Short-term treatment of Mμ with IFN-γ before their addition to T cells caused TBH Mμ to stimulate T-cell proliferation, which suggests that early suppressor molecule production by TBHMø inhibits synthesis or activity of IFN-γ-induced stimulatory monokines. These results show that tumour growth causes Mø to suppress autoreactive T-cell responses by allowing IFN-γ to induce Mø suppressor molecules, which block production or activity of stimulatory monokines.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-3083.1994.tb03336.x
