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.
Article|
March 01 1995
Interferon β, a cofactor in the interferon γ production induced by gram-negative bacteria in mice.
Y Yaegashi,
Y Yaegashi
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Search for other works by this author on:
P Nielsen,
P Nielsen
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Search for other works by this author on:
A Sing,
A Sing
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Search for other works by this author on:
C Galanos,
C Galanos
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Search for other works by this author on:
M A Freudenberg
M A Freudenberg
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Search for other works by this author on:
Y Yaegashi
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
P Nielsen
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
A Sing
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
C Galanos
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
M A Freudenberg
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 181 (3): 953–960.
Citation
Y Yaegashi, P Nielsen, A Sing, C Galanos, M A Freudenberg; Interferon β, a cofactor in the interferon γ production induced by gram-negative bacteria in mice. . J Exp Med 1 March 1995; 181 (3): 953–960. doi: https://doi.org/10.1084/jem.181.3.953
Download citation file: