The role of tumor necrosis factor, interferon-gamma, transforming growth factor-beta, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection.
In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (M phi s) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (ConA)-induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-transforming growth factor-beta (TGF-beta), or anti-interferon-gamma (IFN-gamma) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-gamma, and TGF-beta seem to be related to the full display of the suppressor function of MAC-induced M phi s. However, TNF-alpha and IFN-gamma but not TGF-beta were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-alpha and INF-gamma directly modulated the proliferative response of T cells. On the other hand, both TNF-alpha and IFN-gamma potentiated the effector function of the suppressor M phi s. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminoguanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced M phi s. Moreover, because these M phi s seem to produce a substantial amount of TNF-alpha in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.
D000818:Animals; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016207:Cytokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma