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Infection and Immunity, September 2005, p. 5595-5602, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5595-5602.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cholera Toxin Induces a Transient Depletion of CD8⁺ Intraepithelial Lymphocytes in the Rat Small Intestine as Detected by Microarray and Immunohistochemistry

Carl-Fredrik Flach,¹ Stefan Lange,² Eva Jennische,³ Ivar Lönnroth,^1,2 and Jan Holmgren^1*

Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute,¹ Department of Clinical Bacteriology,² Department of Anatomy and Cell Biology, Göteborg University, Göteborg, Sweden³

Received 26 July 2004/ Returned for modification 4 November 2004/ Accepted 18 May 2005

Cholera toxin (CT), besides causing intestinal hypersecretion after intragastric administration or during cholera infection, affects a multitude of regulatory mechanisms within the gut mucosal network, including T cells. By use of microarray screening, real-time PCR, and immunohistochemistry, we demonstrate here a rapid depletion of jejunal CD8⁺ intraepithelial lymphocytes (IEL) in rats after intragastric CT challenge. This depletion may depend on CT-induced migration of IEL, since it was associated with a progressive decrease of CD8⁺ cells in the epithelium and a contemporary transient increase of such cells, preferentially at the base of the villi, in the lamina propria. A significant decrease in the total number of villous CD8⁺ cells at 6 and 18 h after CT challenge was detected; this possibly reflects an efflux from the jejunal mucosa. The kinetics of the CD8⁺ IEL demonstrate the return to normal intraepithelial position at original numbers already 72 h after the single CT dose. The induced migration seems to be dependent on the enzymatic A-subunit of CT, since challenge with neither sorbitol nor CT B-subunit did mimic the effects of CT on CD8⁺ IEL. Furthermore, a decrease in the level of both RANTES transcript and protein was detected, most likely as a consequence of the CT-induced migration of CD8⁺ IEL. These results point to a complex interaction between CT, epithelial cells, and IEL, resulting in a disturbance of the gut homeostasis, which might have relevance for the strong immunomodulatory effects of intragastrically administered CT.

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* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Göteborg University, Box 435, 40530 Göteborg, Sweden Phone: 46-31-7736200. Fax: 46-31-7736210. E-mail: jan.holmgren{at}microbio.gu.se.

Editor: J. F. Urban, Jr.

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Infection and Immunity, September 2005, p. 5595-5602, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5595-5602.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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