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Infect Immun, July 1998, p. 3120-3127, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Inhibition of Murine Splenic and Mucosal Lymphocyte Function by Enteric Bacterial Products

Carolyn Malstrom and Stephen James*

Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201

Received 14 March 1997/Returned for modification 3 June 1997/Accepted 6 April 1998

Previously we showed that lysates of enteropathogenic Escherichia coli (EPEC) inhibit lymphokine production by mitogen-activated human peripheral blood and lamina propria mononuclear cells. The aims of the present study were to determine whether EPEC-inhibitory factors have similar effects on murine lymphoid populations in order to further delineate the mechanisms of alteration of cytokine production. Preexposure to EPEC lysates inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-gamma ) production by murine spleen cells, but IL-10 production was increased. The inhibition was not due to increased apoptosis and was not blocked by neutralizating antibodies against IL-10 or transforming growth factor beta  (TGF-beta ). EPEC lysates also inhibited mitogen-stimulated IL-2 and IFN-gamma production by CD11b-depleted spleen cells, IL-2 and IL-4 production by intraepithelial and Peyer's patch lymphocytes, IL-2 production by the human T-cell line Jurkat, and antigen-stimulated IL-2 production by murine spleen cells. Lysates obtained from Shiga-like toxin-producing E. coli, E. coli RDEC-1, Citrobacter rodentium, and an EPEC espB insertion mutant all inhibited IL-2 and IL-4 production by mitogen-stimulated lymphoid cells. In conclusion, lysates of EPEC and related bacteria directly inhibit cytokine production by lymphoid cells from multiple sites by a mechanism that does not increase apoptosis or result from secondary effects of IL-10 or TGF-beta .

* Corresponding author. Mailing address: University of Maryland, Baltimore, School of Medicine, 22 South Greene St., Room N3W62, Baltimore, MD 21201. Phone: (410) 328-5780. Fax: (410) 328-8315. E-mail: sjames{at}medicine.ab.umd.edu.

Infect Immun, July 1998, p. 3120-3127, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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