Pertussigen enhances antigen-driven interferon-γ production by sensitized lymphoid cells

doi:10.1016/0008-8749(86)90394-1

Cellular Immunology

Volume 97, Issue 2, February 1986, Pages 238-247

https://doi.org/10.1016/0008-8749(86)90394-1 Get rights and content

Abstract

We have studied the effects on interferon-γ (IFN-γ) production of pertussigen, a protein toxin from Bordetella pertussis that augments and prolongs delayed-type hypersensitivity (DTH) reactions. Lymphoid cell suspensions from immunized mice were incubated with antigen or mitogen, and the culture supernatants were assayed for IFN-γ. The production of IFN-γ on exposure to specific antigen or concanavalin A was greatly enhanced if mice were given pertussigen at the time of immunization. There was no detectable IFN-γ production when cells were exposed to saline or to an irrelevant antigen. The effect of pertussigen on antigen-driven IFN-γ production correlated with its effect on the capacity of the same cell populations to transfer DTH. The enhanced IFN-γ production by cells from mice given pertussigen could not be attributed to an increased antigen-presenting capacity of this cell population. Production of IFN-γ was abolished if the cells were pretreated with emetine, but not with mitomycin C, and the release of IFN-γ was not detected in the first 8 hr of culture. After immunization with pertussigen, IFN-γ was produced by lymph node and spleen cells from 7 days onward and both cell types produced IFN-γ until at least 30 days after immunization. It is suggested that the augmentation of antigenspecific IFN-γ production may contribute to the prolonged DTH reactions induced by pertussigen in vivo.

References (29)

J.J. Munoz et al.
Cell. Immunol
(1984)
R.E. Rocklin et al.
Adv. Immunol
(1980)
E.F. Wheelock
Science (Washington, D.C.)
(1965)
J.A. Green et al.
Science (Washington, D.C.)
(1969)
J.S. Youngner et al.
J. Immunol
(1973)
F. Marcucci et al.
Nature (London)
(1981)
J.L. McKimm-Breschkin et al.
J. Exp. Med
(1982)
P.S. Steeg et al.
J. Exp. Med
(1982)
G.H.W. Wong et al.
J. Immunol
(1983)
P.M. Guyre et al.
J. Clin. Invest
(1983)

B. Perussia et al.

J. Exp. Med

(1983)

C.F. Nathan et al.

J. Exp. Med

(1983)

R.D. Schreiber et al.

J. Immunol

(1983)

J.L. Pace et al.

J. Immunol

(1983)

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^☆: Supported by grants from the National Health and Medical Research Council, Australia.

^1a: W.A.S. was a recipient of a N.H.&M.R.C. Post-Graduate Scholarship.

²: Present address: 3 Rue Marignac, 1206 Géneve, Switzerland.

^1b: P.A.M. was supported by La Foundation Suisse de Bourses de Médecine et Biologie.

³: Present address: Division of Human Immunology, Institute of Medical and Veterinary Science, P.O. Box 14, Rundle Mall, Adelaide 5000, Australia.

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Pertussigen enhances antigen-driven interferon-γ production by sensitized lymphoid cells☆

Abstract

Cell. Immunol

Adv. Immunol

Science (Washington, D.C.)

Science (Washington, D.C.)

J. Immunol

Nature (London)

J. Exp. Med

J. Exp. Med

J. Immunol

J. Clin. Invest

J. Exp. Med

J. Exp. Med

J. Immunol

J. Immunol