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.
Flach
Carl-Fredrik
CF
Department of Medical Microbiology and Immunology, Göteborg University, 40530 Göteborg, Sweden.
Lange
Stefan
S
Jennische
Eva
E
Lönnroth
Ivar
I
Holmgren
Jan
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D002772:Cholera Toxin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D007583:Jejunum / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018946:Chemokine CCL5; D012333:RNA, Messenger; D002772:Cholera Toxin