Interferon beta, a cofactor in the interferon gamma production induced by gram-negative bacteria in mice.
The interferon (IFN) gamma production of splenocytes from closely related C57BL/10ScSn (Sn) and C57BL/10ScCr (Cr) mice was compared. Concanavalin A and CD3 monoclonal antibodies induced high levels of IFN-gamma in both Sn and Cr splenocytes. By contrast, treatment with gram-negative bacteria induced IFN-gamma only in Sn splenocytes; in Cr splenocytes, the IFN-gamma response was heavily impaired. The IFN-gamma induction by bacteria requires the cooperation of IFN-gamma-producing cells with macrophages. Depletion of macrophages from Sn splenocytes resulted in the loss of ability to produce IFN-gamma after bacterial stimulation. Reconstitution with new Sn macrophages restored the IFN-gamma responsiveness, whereas reconstitution with Cr macrophages failed to do so. Normal function of IFN-gamma-producing cells and a defective function of macrophages of Cr mice was demonstrated by evidence showing that whole or macrophage-depleted Cr splenocytes, when supplemented with Sn macrophages, acquire the ability to produce IFN-gamma in response to bacteria. A similar effect was achieved by supplementing Cr splenocytes with supernatants of bacteria-stimulated Sn macrophages or with recombinant murine IFN-beta or IFN-alpha. Preincubation of active macrophage supernatants with antibodies to IFN-beta suppressed the helper activity for Cr splenocytes. Moreover, the bacteria-induced production of IFN-gamma by Sn splenocytes could be inhibited by antibodies to murine IFN-beta. The results provide evidence that IFN-beta is an important cofactor of IFN-gamma induction, which is not induced in Cr mice by gram-negative bacteria.
Yaegashi
Y
Y
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Nielsen
P
P
Sing
A
A
Galanos
C
C
Freudenberg
M A
MA
D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D016899:Interferon-beta / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
D017252:CD3 Complex; D003208:Concanavalin A; D016899:Interferon-beta; D007371:Interferon-gamma