Cholera toxin induces a transient depletion of CD8+ intraepithelial lymphocytes in the rat small intestine as detected by microarray and immunohistochemistry.

• 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.

Nyckelord

Animals

CD8-Positive T-Lymphocytes

immunology

Cholera Toxin

pharmacology

Immunohistochemistry

Intestinal Mucosa

chemistry

cytology

immunology

Jejunum

chemistry

cytology

immunology

Lymphocyte Depletion

Male

Oligonucleotide Array Sequence Analysis

RANTES

biosynthesis

genetics

RNA

Messenger

biosynthesis

Rats

Rats

Sprague-Dawley

Reverse Transcriptase Polymerase Chain Reaction

Publikations- och innehållstyp

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