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The role of tumor necrosis factor, interferon‐γ, Transforming growth factor‐β, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection
Author(s) -
Tomioka Haruaki,
Sato Katsumasa,
Maw Win Win,
Saito Hajime
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.58.6.704
Subject(s) - biology , nitric oxide , tumor necrosis factor alpha , mycobacterium avium complex , tumor necrosis factor α , interferon gamma , transforming growth factor , macrophage , microbiology and biotechnology , immunology , interferon , immune system , endocrinology , in vitro , biochemistry
In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (Mφs) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (Con A)–induced mitogenesis of splenocytes (SPCs). When either anti‐tumor necrosis factor (TNF), anti‐Transforming growth factor‐β (TGF‐β), or anti‐interferon‐γ (IFN‐γ) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti‐TNF, anti‐IFN‐γ, and anti‐TGF‐β antibodies. By contrast, neither anti‐interleukin‐6 (IL‐6) nor anti‐IL‐10 antibody exerted such a blocking effect. Therefore, TNF, IFN‐γ, and TGF‐β seem to be related to the full display of the suppressor function of MAC‐induced Mφs. However, TNF‐α and IFN‐γ but not TGF‐β were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF‐α and IFN‐γ directly modulated the proliferative response of T cells. On the other hand, both TNF‐α and IFN‐γ potentiated the effector function of the suppressor Mφs. Because their suppressor activity was severely reduced by N G ‐monomethyl‐L‐arginine and aminognanidine, nitric oxide (NO) synthase inhibitors, an NO‐dependent mechanism is important for the expression of the immunosuppressive function of MAC‐induced Mφs. Moreover, because these Mφs seem to produce a substantial amount of TNF‐α in membrane‐bound form, cell‐to‐cell contact might be needed for efficient expression of their suppressor action on target T cells.